VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY COURSE DETAILS Faculty Name: Dr. Smila K. H Faculty Code: HTS 846 Subject Name: Neurobiology and Cognitive Sciences Course Code:BT6018 Class: Dept-Biotechnology Year/IV , Semester : VII COURSE OBJECTIVES Course Outcomes: On completion of this course, the students will be able to CO No Course Outcomes Knowledge Level

C409.1 Know the anatomy and organization of nervous systems. K2 C409.2 Understand the function of nervous systems. K2

C409.3 Analyze how drugs affect cellular function in the nervous system. K4

C409.4 Understand the basic mechanisms of sensations K2

C409.5 Understand the basic mechanisms associated with behavioral science. K2

MAPPING BETWEEN CO AND PO, PSO WITH CORRELATION LEVEL 1/2/3

BT6018 PO1 PO2 PO3 PO4 PO5 PO6 PO7 PO8 PO9 PO10 PO11 PO12

C409.1 ------2 2 - - - 1 C409.2 ------2 2 - - - - C409.3 ------2 2 - - - - C409.4 ------3 2 - - - 1 C409.5 ------3 2 - - - 1

C.No PO1 PO 2 PO 3 PO 4 PO 5 PO 6 PO7 PO 8 PO 9 PO 10 PO 11 PO 12

C409 ------2 2 - - - 1

Mapping Relevancy 3 – Substantial (Highly relevant) 2 – Moderate (Medium) 1 – Slight (Low) Course delivery methods  Class room lecture - Black board  Audio & Video Tools  ―Real-World‖  Brainstorm  Classes Outside the Classroom

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

Assessment methods Direct Assessment Indirect Assessment CIA Student feed back End semester examination Course exit survey Assigments and Seminar SYLLABUS BT6018 NEUROBIOLOGY AND COGNITIVE SCIENCES L T P C 3 0 0 3 OBJECTIVES: To enable the students  To know the general organization of and physiological and cognitive processes.  To apply the molecular, cellular, and cognitive bases of learning and .

UNIT I NEUROANATOMY 9 What are central and peripheral nervous systems; Structure and function of ; types of neurons; Synapses; Glial cells; myelination; Blood Brain barrier; Neuronal differentiation; Characterization of neuronal cells; Meninges and Cerebrospinal fluid; . UNIT II NEUROPHYSIOLOGY9 Resting and action potentials; Mechanism of action potential conduction; Voltage dependent channels; nodes of Ranvier; Chemical and electrical synaptic transmission; information representation and coding by neurons. UNIT III NEUROPHARMACOLOGY 9 Synaptic transmission, neurotransmitters and their release; fast and slowneurotransmission; characteristics of neurites; hormones and their effect on neuronalfunction. UNIT IV APPLIED NEUROBIOLOGY 9 Basic mechanisms of sensations like touch, pain, smell and taste; neurologicalmechanisms of vision and audition; skeletal muscle contraction. UNIT V BEHAVIOUR SCIENCE 9 Basic mechanisms associated with motivation; control of feeding, sleep, hearing andmemory; Disorders associated with the nervous system. TOTAL: 45 PERIODS OUTCOMES: Upon completion of this course, students will be able:  To know the anatomy and organization of nervous systems.  To understand the function of nervous systems.  To analyze how drugs affect cellular function in the nervous system.  To understand the basic mechanisms associated with behavioral science.

TEXTBOOKS: 1. Mathews G.G. Neurobiology, 2nd edition, Blackwell Science, UK, 2000. 2. Gordon M. Shepherd G.M, and Shepherd Neurobiology, 3rd Edition Oxford UniversityPress, USA, 1994

REFERENCE: 1. Mason P., Medical Neurobiology, Oxford University Press, 2011.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

UNIT – I PART – A 1. Write short notes on meninges. Meninges is the system of membranes which envelopes the central nervous system. The meninges consist of three layers: the dura mater, the arachnoid mater, and the pia mater. The primary function of the meninges and of the cerebrospinal fluid is to protect the central nervous system. Dura mater The dura mater is a thick, durable membrane, closest to the skull. It consists of two layers, the periosteal layer which lies closest to the calvaria, and the inner meningeal layer which lies closer to the brain. Arachnoid mater The middle element of the meninges is the arachnoid mater, so named because of its spider web-like appearance. It provides a cushioning effect for the central nervous system. The arachnoid mater exists as a thin, transparent membrane. It is composed of fibrous tissue and, like the pia mater. The arachnoid and pia mater are sometimes together called the Pia mater The pia or pia mater is a very delicate membrane. It is the meningeal envelope which firmly adheres to the surface of the brain and spinal cord. As such it follows all the minor contours of the brain (gyri and sulci). It is a very thin membrane composed of fibrous tissue covered on its outer surface by a sheet of flat cells thought to be impermeable to fluid. The subarachnoid space is the space which normally exists between the arachnoid and the pia mater, which is filled with cerebrospinal fluid. 2. Give the functions of Brain. The brain monitors and regulates the body's actions and reactions. It continuously receives sensory information, and rapidly analyzes these data and then responds, controlling bodily actions and functions. The brainstem controls breathing, heart rate, and other autonomic processes that are independent of conscious brain functions. The neocortex is the center of higher-order thinking, learning, and memory. The is responsible for the body's balance, posture, and the coordination of movement. 3. Write short notes on cerebrospinal fluid. Cerebrospinal fluid (CSF), Liquor cerebrospinalis, is a clear bodily fluid that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord. In essence, the brain "floats" in it. The CSF occupies the space between the arachnoid mater (the middle layer of the brain cover, meninges), and the pia mater (the layer of the meninges closest to the brain). It constitutes the content of all intra-cerebral (inside the brain, cerebrum) ventricles, cisterns, and sulci (singular sulcus), as well as the central canal of the spinal cord. It acts as a "cushion" or buffer for the cortex, providing a basic mechanical and immunological protection to the brain inside the skull. The CSF is produced at a rate of 500 ml/day. Since the brain can contain only 135 to 150 ml, large amounts are drained primarily into the blood through arachnoid granulations in the superior sagittal sinus. Functions CSF serves four primary purposes: 1. Buoyancy:

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

2. Protection: CSF protects the brain tissue from injury when jolted or hit. 3. Chemical stability: CSF flows throughout the inner ventricular system in the brain and is absorbed back into the bloodstream, rinsing the metabolic waste from the central nervous system through the blood-brain barrier. 4. Prevention of brain ischemia: The prevention of brain ischemia is made by decreasing the amount of CSF in the limited space inside the skull. This decreases total intracranial pressure and facilitates blood perfusion. 5. CSF can be tested for the diagnosis of a variety of neurological diseases.[10] It is usually obtained by a procedure called lumbar puncture. 4. Name the lobes of the cerebrum The four lobes of the Outwardly, the cerebral cortex is nearly symmetrical, with left and right hemispheres. Anatomists conventionally divide each hemisphere into four "lobes", the:  Frontal lobe   Occipital lobe  Temporal lobe 5. Define . A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous system, which includes the brain, spinal cord, and peripheral ganglia. A number of specialized types of neurons exist: sensory neurons respond to touch, sound, light and numerous other stimuli affecting cells of the sensory organs that then send signals to the spinal cord and brain 6. Write short notes on Glial cells. Glial cells, sometimes called neuroglia or simply glia (Greek for "glue"), are non- neuronal cells that maintain homeostasis, form myelin, and provide support and protection for the brain's neurons. In the human brain, there is roughly one glia for every neuron with a ratio of about two neurons for every three glia in the cerebral gray matter. 7. What is myelin? Myelin is a dielectric (electrically insulating) material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a glial cell 8. Write short notes on Blood Brain Barrier [BBB]. The blood-brain barrier (BBB) is a separation of circulating blood and cerebrospinal fluid (CSF) in the central nervous system (CNS). It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion of microscopic objects (e.g. bacteria) and large or hydrophilic molecules into the CSF, while allowing the diffusion of small hydrophobic molecules (O2, hormones, CO2). Cells of the barrier actively transport metabolic products such as glucose across the barrier with specific proteins. 9. Classify neuron.(By Function) a)Sensory Receptor Cells:Detect energy changes in the environment, Rods and cones in the retina of the eye, Hair cells in the cochlea of the ear, Olfactory receptors in the nose, etc.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES b) Sensory Neurons, or Afferent Neurons: Conduct sensory information toward the CNS,Found in peripheral nervous system. 10. Write the functions of meninges. The meninges functions primarily to protect and support the central nervous system (CNS). It connects the brain and spinal cord to the skull and spinal canal. The meninges forms a protective barrier that safeguards the sensitive organs of the CNS against trauma. It also contains an ample supply of blood vessels that deliver blood to CNS tissue. Another important function of the meninges is that it produces cerebrospinal fluid. This clear fluid fills the cavities of the cerebral ventricles and surrounds the brain and spinal cord. Cerebrospinal fluid protects and nourishes CNS tissue by acting as a shock absorber, by circulating nutrients, and by getting rid of waste products. c)Interneurons, or Internuncial Cells, or Association Neurons: Interconnect sensory and motor, neurons, and interneurons, Information processing and decision making function,Most common type of neuron by far,Intrinsic neurons (usually) d) Motor Neurons, or Efferent Neurons, or Effector Neurons: Conduct commands to muscles and glands, Found in spinal cord, brain stem, and ANS ganglia e)Neurosecretory Cells: Secrete hormones and similar substances, Hypothalamus of brain, adrenal medulla gland, etc. 11. List the basic parts of neurons. Neurons (nerve cells) have three parts that carry out the functions of communication and integration: dendrites, axons, and axon terminals. They have a fourth part the cell body or soma, which carries out the basic life processes of neurons. 12. Describe synapses. In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron. 13. List the function of neurons a)Receive signals (or information). b) Integrate incoming signals (to determine whether or not the information should be passed along). c) Communicate signals to target cells (other neurons or muscles or glands). 14. Differentiate CNS and PNS. a) CNS refers to the Central Nervous System whereas PNS refers to the Peripheral Nervous System. b) The Central Nervous System comprises of the brain and the spinal cord whereas the Peripheral Nervous System comprises of the autonomic nervous system and the somatic nervous system. c) The CNS handles involuntary information while the PNS handles voluntary information. 15. Discuss the functions of myelin sheath. Neurones can either be myelinated - they are sorrounded by a myelin sheath, or unmyelinated - they are not surrounded by a myelin sheath. The myelin sheath is made up of Schwann cells and there are gaps in the sheath called the Nodes of Ranvier. The main functions of the myelin sheath are: 1) It acts as an electrical insulator for the neurone - it prevents electrical impulses travelling through the sheath.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

2) The sheath prevents the movement of ions into or out of the neurone/ it prevents depolarisation. 3) It speeds up conduction/ transmission of an electrical impulse in the neurone - impulses cannot travel through the sheath (the sheath acts as an electrical insulator), instead, impulses 'jump' from a gap in the myelin sheath to another gap (it jumps from one Node of Ranvier to another Node). This is a process called Saltatory Conduction. 16. What are Nodes of Ranvier? Nodes of Ranvier, also known as myelin sheath gaps, are periodic gaps in the insulating myelin sheaths of myelinated axons where the axonal membrane is exposed to the extracellular space. Nodes of Ranvier are uninsulated and highly enriched in ion channels, allowing them to participate in the exchange of ions required to regenerate the action potential. Nerve conduction in myelinated axons is referred to as saltatory conduction because of the manner in which the action potential seems to "jump" from one node to the next along the length of the axon. This results in faster conduction of the action potential. 17. Give the structure of neuron. Neurons are nerve cells which are the functional units of the nervous system. The three main parts of a neuron are dendrite, cell body and axon.

Dendrite: It detects information and conducts the messages towards the cell body. Cell body: It contains , mitochondria, and other cell organelles. It maintains the growth of the cell. Axon: It conducts messages away from the cell body and pass to the next neuron. 18. List out the types of Glial cells. The glial cells surround neurons and provide support for and insulation between them. Glial cells are the most abundant cell types in the central nervous system. Types of glial cells include oligodendrocytes, astrocytes, ependymal cells, Schwann cells, microglia, and satellite cells. 19. Name the supporting cells of CNS. Astrocytes: Astrocytes play a variety of roles within the CNS, from maintaining structure of neural and vascular tissue, providing nourishment to neurons, to helping regulate local blood flow within the brain. Microglia: Microglia are named fittingly, as they comprise the smallest of the neuroglia cell types. Their main role within the CNS is to engulf and digest neurons that are either dead or dying. Ependymal cells: Ependymal cells are responsible for the production, monitoring and secretion of cerebrospinal fluid (CSF) with the central nervous system. Oligodendrocytes: Oligodendrocytes serve a structural purpose within neuronal networks and they also function to produce myelin. 20. Name the supporting cells of CNS. Schwann Cells: Schwann cells are located throughout the PNS. Schwann cells wrap themselves

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES around the axons of PNS neurons, providing insulation and increasing the efficiency with which they transmit impulses. Satellite Cells: Satellite cells perform a similar role to the astrocytes of the CNS. They support and cushion the neurons of the PNS, and they also supply them with nutrients. Processes: The processes (also called projections or fibers) of neurons are often very numerous and range in length from a fraction of the length of the cell body to up to over a meter in length. 21. Write a short note on spinal cord. The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column. The brain and spinal cord together make up the central nervous system (CNS). 22. Give the functions of Spinal cord. The Major Functions of The Spinal Cord are: Electrical communication. Electrical currents travel up and down the spinal cord, sending signals which allow different segments of the body to communicate with the brain. Walking. While a person walks, a collection of muscle groups in the legs are constantly contracting. The action of taking step after step may seem incredibly simple to us since we have been doing it all of our lives, but there are actually a lot of factors that have to be coordinated properly to allow this motion to occur. This central pattern generators in the spinal cord are made up of neurons which send signals to the muscles in the legs, making them extend or contract, and produce the alternating movements which occur when a person walks. Reflexes. Reflexes are involuntary responses resulting from stimuli involving the brain, spinal cord, and nerves of the peripheral nervous system. 23. Write a short note on Spinal nerves. Spinal nerves are what allow the spinal cord and the rest of the body to communicate. A nerve is an organ shaped like a small cord that is made up of several axons that are bound together. There are 31 pairs of spinal nerves:  8 are cervical nerves located in the neck  12 are thoracic nerves located in the chest  5 are lumbar nerves located in the abdomen  5 are sacral nerves located in the pelvis  1 is the coccygeal nerve located in the tailbone.

PART – B 1. Explain the central nervous system The central nervous system (CNS) is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish. It contains the majority of the nervous system and consists of the brain and the spinal cord. Some classifications also include the retina and the cranial nerves in the CNS. Together with the peripheral nervous system, it has a fundamental role in the control of behavior. The CNS is contained within the dorsal cavity, with the brain in the cranial cavity and the spinal cord in the spinal cavity. Brain In vertebrates, the brain is protected by the skull, while the spinal cord is protected by the vertebrae, and both are enclosed in the meninges.During early development of the vertebrate

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES embryo, a longitudinal groove on the neural plate gradually deepens as ridges on either side of the groove (the neural folds) become elevated, and ultimately meet, transforming the groove into a closed tube, the ectodermal wall of which forms the rudiment of the nervous system. This tube initially differentiates into three vesicles (pockets): the prosencephalon at the front, the mesencephalon, and, between the mesencephalon and the spinal cord, the rhombencephalon. (By six weeks in the human embryo) the prosencephalon then divides further into the telencephalon and diencephalon; and the rhombencephalon divides into the metencephalon and myelencephalon. The human brain is the center of the human nervous system. Enclosed in the cranium, it has the same general structure as the of other mammals, but is over three times as large as the brain of a typical mammal with an equivalent body size. Most of the expansion comes from the cerebral cortex, a convoluted layer of neural tissue that covers the surface of the . Especially expanded are the frontal lobes, which are associated with executive functions such as self-control, planning, reasoning, and abstract thought. The portion of the brain devoted to vision is also greatly enlarged in human beings. Brain evolution, from the earliest shrewlike mammals through primates to hominids, is marked by a steady increase in encephalization, or the ratio of brain to body size. The human brain has been estimated to contain 50–100 billion (1011) neurons, of which about 10 billion (1010) are cortical pyramidal cells. These cells pass signals to each other via as many as 1000 trillion (1015, 1quadrillion) synaptic connections. However, recent research has shown that the modern human brain has actually been shrinking over the last 28,000 years. The brain monitors and regulates the body's actions and reactions. It continuously receives sensory information, and rapidly analyzes these data and then responds, controlling bodily actions and functions. The brainstem controls breathing, heart rate, and other autonomic processes that are independent of conscious brain functions. The neocortex is the center of higher-order thinking, learning, and memory. The cerebellum is responsible for the body's balance, posture, and the coordination of movement. The adult human brain weighs on average about 3 lb (1.5 kg) with a size (volume) of around 1130 cubic centimetres (cm3) in women and 1260 cm3 in men, although there is substantial individual variation. Men with the same body height and body surface area as women have on average 100g heavier brains, although these differences do not correlate in any simple way with gray matter neuron counts or with overall measures of cognitive performance. Neanderthals, an extinct subspecies of modern humans, had larger brains at adulthood than present-day humans. The brain is very soft, having a consistency similar to soft gelatin or firm tofu. Despite being referred to as "grey matter", the live cortex is pinkish-beige in color and slightly off-white in the interior. At the age of 20, a man has around 176,000 km and a woman about 149,000 km of myelinated axons in their brains. The cerebral hemispheres form the largest part of the human brain and are situated above most other brain structures. They are covered with a cortical layer with a convoluted topography. Underneath the cerebrum lies the brainstem, resembling a stalk on which the cerebrum is attached. At the rear of the brain, beneath the cerebrum and behind the brainstem, is the cerebellum, a structure with a horizontally furrowed surface that makes it look different from any other brain area. The same structures are present in other mammals, although the cerebellum is not so large relative to the rest of the brain. As a rule, the smaller the cerebrum, the less convoluted the cortex. The cortex of a rat or mouse is almost completely smooth. The cortex of a

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES dolphin or whale, on the other hand, is more convoluted than the cortex of a human. The dominant feature of the human brain is corticalization. The cerebral cortex in humans is so large that it overshadows every other part of the brain. A few subcortical structures show alterations reflecting this trend. The cerebellum, for example, has a medial zone connected mainly to subcortical motor areas, and a lateral zone connected primarily to the cortex. In humans the lateral zone takes up a much larger fraction of the cerebellum than in most other mammalian species. Corticalization is reflected in function as well as structure. In a rat, surgical removal of the entire cerebral cortex leaves an animal that is still capable of walking around and interacting with the environment. In a human, comparable cerebral cortex damage produces a permanent state of coma. The amount of association cortex, relative to the other two categories, increases dramatically as one goes from simpler mammals, such as the rat and the cat, to more complex ones, such as the chimpanzee and the human. The cerebral cortex is essentially a sheet of neural tissue, folded in a way that allows a large surface area to fit within the confines of the skull. Each , in fact, has a total surface area of about 1.3 square feet. Anatomists call each cortical fold a sulcus, and the smooth area between folds a gyrus. Cortical divisions Four lobes

Figure: The four lobes of the cerebral cortex Outwardly, the cerebral cortex is nearly symmetrical, with left and right hemispheres. Anatomists conventionally divide each hemisphere into four "lobes", the:  Frontal lobe  Parietal lobe  Occipital lobe  Temporal lobe Spinal cord The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain (the medulla oblongata specifically). The brain and spinal cord together make up the central nervous system. The spinal cord begins at the Occipital bone and extends down to the space between the first and second lumbar vertebrae; it does not extend the entire length of the vertebral column. It is around 45 cm (18 in) in men and around 43 cm (17 in) long in women. Also, the spinal cord has a varying width, ranging from 1/2 inch thick in the cervical

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES and lumbar regions to 1/4 inch thick in the thoracic area. The enclosing bony vertebral column protects the relatively shorter spinal cord. The spinal cord functions primarily in the transmission of neural signals between the brain and the rest of the body but also contains neural circuits that can independently control numerous reflexes and central pattern generators. The spinal cord has three major functions: A. Serve as a conduit for motor information, which travels down the spinal cord. B. Serve as a conduit for sensory information, which travels up the spinal cord. C. Serve as a center for coordinating certain reflexes. 2 Explain the peripheral nervous system. The peripheral nervous system, or PNS, consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system (CNS) to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood-brain barrier, leaving it exposed to toxins and mechanical injuries. The peripheral nervous system is divided into the somatic nervous system and the autonomic nervous system; some textbooks also include sensory systems. There are two types of neurons, carrying nerve impulses in different directions. These two groups of neurons are:  The sensory neurons are afferent neurons which relay nerve impulses toward the central nervous system.  The motor neurons are efferent neurons which relay nerve impulses away from the central nervous system. Function The peripheral nervous system is functionally as well as structurally divided into the somatic nervous system and autonomic nervous system. The somatic nervous system is responsible for coordinating the body movements, and also for receiving external stimuli. It is the system that regulates activities that are under conscious control. The autonomic nervous system is then split into the sympathetic division, parasympathetic division, and enteric division. The sympathetic nervous system responds to impending danger, and is responsible for the increase of one's heartbeat and blood pressure, among other physiological changes, along with the sense of excitement one feels due to the increase of adrenaline in the system. ("fight or flight" responses). The parasympathetic nervous system, on the other hand, is evident when a person is resting and feels relaxed, and is responsible for such things as the constriction of the pupil, the slowing of the heart, the dilation of the blood vessels, and the stimulation of the digestive and genitourinary systems. ("rest and digest" responses). The role of the enteric nervous system is to manage every aspect of digestion, from the esophagus to the stomach, small intestine and colon. Specific nerves and plexi Ten out of the twelve cranial nerves originate from the brainstem, and mainly control the functions of the anatomic structures of the head with some exceptions. The nuclei of cranial nerves I and II lie in the forebrain and , respectively, and are thus not considered to be true cranial nerves. CN X (10) receives visceral sensory information from the thorax and abdomen, and CN XI (11) is responsible for innervating the sternocleidomastoid and trapezius muscles, neither of which is exclusively in the head. Spinal nerves take their origins from the spinal cord. They control the functions of the rest of the body. In humans, there are 31 pairs of spinal nerves: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral and 1 coccygeal. In the cervical region, the spinal nerve roots come out above the corresponding vertebrae (i.e. nerve root between the skull and 1st cervical vertebrae is called

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES spinal nerve C1). From the thoracic region to the coccygeal region, the spinal nerve roots come out below the corresponding vertebrae. It is important to note that this method creates a problem when naming the spinal nerve root between C7 and T1 (so it is called spinal nerve root C8). In the lumbar and sacral region, the spinal nerve roots for travel within the dural sac and they travel below the level of L2 as the cauda equina. Cervical spinal nerves (C1-C4) Further information: Cervical plexus The first 4 cervical spinal nerves, C1 through C4, split and recombine to produce a variety of nerves that subserve the neck and back of head. Spinal nerve C1 is called the suboccipital nerve which provides motor innervation to muscles at the base of the skull. C2 and C3 form many of the nerves of the neck, providing both sensory and motor control. These include the greater occipital nerve which provides sensation to the back of the head, the lesser occipital nerve which provides sensation to the area behind the ears, the greater auricular nerve and the lesser auricular nerve. See occipital neuralgia. The phrenic nerve arises from nerve roots C3, C4 and C5. It innervates the diaphragm, enabling breathing. If the spinal cord is transected above C3, then spontaneous breathing is not possible. Brachial plexus (C5-T1) The last four cervical spinal nerves, C5 through C8, and the first thoracic spinal nerve, T1,combine to form the brachial plexus, or plexus brachialis, a tangled array of nerves, splitting, combining and recombining, to form the nerves that subserve the arm and upper back. Although the brachial plexus may appear tangled, it is highly organized and predictable, with little variation between people. See brachial plexus injuries. Neurotransmitters The main neurotransmitters of the peripheral nervous system are acetylcholine and noradrenaline. However, there are several other neurotransmitters as well, jointly labeled Non- noradrenergic, non-cholinergic (NANC) transmitters. Examples of such transmitters include non- peptides: ATP 3. Give a detailed account on neuron A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous system, which includes the brain, spinal cord, and peripheral ganglia. A number of specialized types of neurons exist: sensory neurons respond to touch, sound, light and numerous other stimuli affecting cells of the sensory organs that then send signals to the spinal cord and brain. Motor neurons receive signals from the brain and spinal cord, cause muscle contractions, and affect glands. Interneurons connect neurons to other neurons within the same region of the brain or spinal cord. A typical neuron possesses a cell body (often called the soma), dendrites, and an axon. Dendrites are filaments that arise from the cell body, often extending for hundreds of micrometres and branching multiple times, giving rise to a complex "dendritic tree". An axon is a special cellular filament that arises from the cell body at a site called the axon hillock and travels for a distance, as far as 1 m in humans or even more in other species. The cell body of a neuron frequently gives rise to multiple dendrites, but never to more than one axon, although the axon may branch hundreds of times before it terminates. At the majority of synapses, signals are sent from the axon of one neuron to a dendrite of another. There are, however, many exceptions

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES to these rules: neurons that lack dendrites, neurons that have no axon, synapses that connect an axon to another axon or a dendrite to another dendrite, etc. All neurons are electrically excitable, maintaining voltage gradients across their membranes by means of metabolically driven ion pumps, which combine with ion channels embedded in the membrane to generate intracellular-versus-extracellular concentration differences of ions such as sodium, potassium, chloride, and calcium. Changes in the cross- membrane voltage can alter the function of voltage-dependent ion channels. If the voltage changes by a large enough amount, an all-or-none electrochemical pulse called an action potential is generated, which travels rapidly along the cell's axon, and activates synaptic connections with other cells when it arrives. Neurons of the adult brain do not generally undergo cell division, and usually cannot be replaced after being lost, although there are a few known exceptions. In most cases they are generated by special types of stem cells, although astrocytes (a type of glial cell) have been observed to turn into neurons as they are sometimes pluripotent. A neuron is a special type of cell that is found in the bodies of most animals (all members of the group Eumetazoa, to be precise—this excludes only sponges and a few other very simple animals). The features that define a neuron are electrical excitability and the presence of synapses, which are complex membrane junctions used to transmit signals to other cells. The body's neurons, plus the glial cells that give them structural and metabolic support, together constitute the nervous system. In vertebrates, the majority of neurons belong to the central nervous system, but some reside in peripheral ganglia, and many sensory neurons are situated in sensory organs such as the retina and cochlea. Although neurons are very diverse and there are exceptions to nearly every rule, it is convenient to begin with a schematic description of the structure and function of a "typical" neuron. A typical neuron is divided into three parts: the soma or cell body, dendrites, and axon. The soma is usually compact; the axon and dendrites are filaments that extrude from it. Dendrites typically branch profusely, getting thinner with each branching, and extending their farthest branches a few hundred micrometres from the soma. The axon leaves the soma at a swelling called the axon hillock, and can extend for great distances, giving rise to hundreds of branches. Unlike dendrites, an axon usually maintains the same diameter as it extends. The soma may give rise to numerous dendrites, but never to more than one axon. Synaptic signals from other neurons are received by the soma and dendrites; signals to other neurons are transmitted by the axon. A typical synapse, then, is a contact between the axon of one neuron and a dendrite or soma of another. Synaptic signals may be excitatory or inhibitory. If the net excitation received by a neuron over a short period of time is large enough, the neuron generates a brief pulse called an action potential, which originates at the soma and propagates rapidly along the axon, activating synapses onto other neurons as it goes. Many neurons fit the foregoing schema in every respect, but there are also exceptions to most parts of it. There are no neurons that lack a soma, but there are neurons that lack dendrites, and others that lack an axon. Furthermore, in addition to the typical axodendritic and axosomatic synapses, there are axoaxonic (axon-to-axon) and dendrodendritic (dendrite-to-dendrite) synapses. The key to neural function is the synaptic signalling process, which is partly electrical and partly chemical. The electrical aspect depends on properties of the neuron's membrane. Like all animal cells, every neuron is surrounded by a plasma membrane, a bilayer of lipid molecules

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES with many types of protein structures embedded in it. A lipid bilayer is a powerful electrical insulator, but in neurons, many of the protein structures embedded in the membrane are electrically active. These include ion channels that permit electrically charged ions to flow across the membrane, and ion pumps that actively transport ions from one side of the membrane to the other. Most ion channels are permeable only to specific types of ions. Some ion channels are voltage gated, meaning that they can be switched between open and closed states by altering the voltage difference across the membrane. Others are chemically gated, meaning that they can be switched between open and closed states by interactions with chemicals that diffuse through the extracellular fluid. The interactions between ion channels and ion pumps produce a voltage difference across the membrane, typically a bit less than 1/10 of a volt at baseline. This voltage has two functions: first, it provides a power source for an assortment of voltage-dependent protein machinery that is embedded in the membrane; second, it provides a basis for electrical signal transmission between different parts of the membrane. Neurons communicate by chemical and electrical synapses in a process known as synaptic transmission. The fundamental process that triggers synaptic transmission is the action potential, a propagating electrical signal that is generated by exploiting the electrically excitable membrane of the neuron. This is also known as a wave of depolarization. Anatomy and histology

Figure:

Diagram of a typical myelinated vertebrate motoneuron Neurons are highly specialized for the processing and transmission of cellular signals. Given the diversity of functions performed by neurons in different parts of the nervous system, there is, as expected, a wide variety in the shape, size, and electrochemical properties of neurons. For instance, the soma of a neuron can vary from 4 to 100 micrometers in diameter.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 The soma is the central part of the neuron. It contains the nucleus of the cell, and therefore is where most protein synthesis occurs. The nucleus ranges from 3 to 18 micrometers in diameter.  The dendrites of a neuron are cellular extensions with many branches, and metaphorically this overall shape and structure is referred to as a dendritic tree. This is where the majority of input to the neuron occurs.  The axon is a finer, cable-like projection which can extend tens, hundreds, or even tens of thousands of times the diameter of the soma in length. The axon carries nerve signals away from the soma (and also carries some types of information back to it). Many neurons have only one axon, but this axon may—and usually will—undergo extensive branching, enabling communication with many target cells. The part of the axon where it emerges from the soma is called the axon hillock. Besides being an anatomical structure, the axon hillock is also the part of the neuron that has the greatest density of voltage- dependent sodium channels. This makes it the most easily-excited part of the neuron and the spike initiation zone for the axon: in electrophysiological terms it has the most negative action potential threshold. While the axon and axon hillock are generally involved in information outflow, this region can also receive input from other neurons.  The axon terminal contains synapses, specialized structures where neurotransmitter chemicals are released in order to communicate with target neurons. Nerve cell bodies stained with basophilic dyes show numerous microscopic clumps of Nissl substance (named after German psychiatrist and neuropathologist Franz Nissl, 1860–1919), which consists of rough endoplasmic reticulum and associated ribosomal RNA. The prominence of the Nissl substance can be explained by the fact that nerve cells are metabolically very active, and hence are involved in large amounts of protein synthesis. Classification of neuron. Neurons exist in a number of different shapes and sizes and can be classified by their morphology and function. The anatomist Camillo Golgi grouped neurons into two types; type I with long axons used to move signals over long distances and type II with short axons, which can often be confused with dendrites. Type I cells can be further divided by where the cell body or soma is located. The basic morphology of type I neurons, represented by spinal motor neurons, consists of a cell body called the soma and a long thin axon which is covered by the myelin sheath. Around the cell body is a branching dendritic tree that receives signals from other neurons. The end of the axon has branching terminals (axon terminal) that release neurotransmitters into a gap called the synaptic cleft between the terminals and the dendrites of the next neuron.  Unipolar or pseudounipolar: dendrite and axon emerging from same process.  Bipolar: axon and single dendrite on opposite ends of the soma. Multipolar: more than two dendrites: Furthermore, some unique neuronal types can be identified according to their location in the nervous system and distinct shape. Some examples are:  Basket cells, interneurons that form a dense plexus of terminals around the soma of target cells, found in the cortex and cerebellum.  Betz cells, large motor neurons.  Medium spiny neurons, most neurons in the corpus .  Purkinje cells, huge neurons in the cerebellum, a type of Golgi I multipolar neuron.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 Pyramidal cells, neurons with triangular soma, a type of Golgi I.  Renshaw cells, neurons with both ends linked to alpha motor neurons.  Granule cells, a type of Golgi II neuron.  Anterior horn cells, motoneurons located in the spinal cord. Functional classification  Afferent neurons convey information from tissues and organs into the central nervous system and are sometimes also called sensory neurons.  Efferent neurons transmit signals from the central nervous system to the effector cells and are sometimes called motor neurons.  Interneurons connect neurons within specific regions of the central nervous system. Afferent and efferent can also refer generally to neurons which, respectively, bring information to or send information from the brain region. Classification by neurotransmitter production Neurons differ in the type of neurotransmitter they manufacture. Some examples are:  Cholinergic neurons—acetylcholine. Acetylcholine is released from presynaptic neurons into the synaptic cleft. It acts as a ligand for both ligand-gated ion channels and metabotropic (GPCRs) muscarinic receptors. Nicotinic receptors, are pentameric ligand- gated ion channels composed of alpha and beta subunits that bind nicotine. Ligand binding opens the channel causing influx of Na+ depolarization and increases the probability of presynaptic neurotransmitter release.  GABAergic neurons—gamma aminobutyric acid. GABA is one of two neuroinhibitors in the CNS, the other being Glycine. GABA has a homologous function to ACh, gating anion channels that allow Cl- ions to enter the post synaptic neuron. Cl- causes hyperpolarization within the neuron, decreasing the probability of an action potential firing as the voltage becomes more negative ( that for an action potential to fire, a positive voltage threshold must be reached).  Serotonergic neurons—serotonin. Serotonin,(5-Hydroxytryptamine, 5-HT), can act as excitatory or inhibitory. Of the four 5-HT receptor classes, 3 are GPCR and 1 is ligand gated cation channel. Serotonin is synthesized from tryptophan by tryptophan hydroxylase, and then further by aromatic acid decarboxylase. A lack of 5-HT at postsynaptic neurons has been linked to depression. Drugs that block the presynaptic serotonin transporter are used for treatment, such as Prozac and Zoloft. 4. Describe synapse In the nervous system, a synapse is a junction that permits a neuron to pass an electrical or chemical signal to another cell (neural or otherwise). The word "synapse" comes from "synaptein", which Sir Charles Scott Sherrington and colleagues coined from the Greek "syn-" ("together") and "haptein" ("to clasp"). Synapses are essential to neuronal function: neurons are cells that are specialized to pass signals to individual target cells, and synapses are the means by which they do so. At a synapse, the plasma membrane of the signal-passing neuron (the presynaptic neuron) comes into close apposition with the membrane of the target (postsynaptic) cell. Both the presynaptic and postsynaptic sites contain extensive arrays of molecular machinery that link the two membranes together and carry out the signaling process. In many synapses, the presynaptic part is located on an axon, but some presynaptic sites are located on a dendrite or soma. There are two fundamentally different types of synapse:

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 In a chemical synapse, the presynaptic neuron releases a chemical called a neurotransmitter that binds to receptors located in the postsynaptic cell, usually embedded in the plasma membrane. Binding of the neurotransmitter to a receptor can affect the postsynaptic cell in a wide variety of ways.  In an electrical synapse, the presynaptic and postsynaptic cell membranes are connected by channels that are capable of passing electrical current, causing voltage changes in the presynaptic cell to induce voltage changes in the postsynaptic cell.

Neurotransmission (Latin: transmissio = passage, crossing; from transmitto = send, let through), also called synaptic transmission, is an electrical movement within synapses caused by a propagation of nerve impulses. As each nerve cell receives neurotransmitter from the presynaptic neuron, or terminal button, to the postsynaptic neuron, or dendrite, of the second neuron, it sends it back out to several neurons, and they do the same, thus creating a wave of energy until the pulse has made its way across an organ or specific area of neurons. Nerve impulses are essential for the propagation of signals. These signals are sent to and from the central nervous system via efferent and afferent neurons in order to coordinate smooth, skeletal and cardiac muscles, bodily secretions and organ functions critical for the long-term survival of multicellular vertebrate organisms such as mammals. Neurons form networks through which nerve impulses travel. Each neuron receives as many as 15,000 connections from other neurons. Neurons do not touch each other; they have contact points called synapses. A neuron transports its information by way of a nerve impulse. When a nerve impulse arrives at the synapse, it releases neurotransmitters, which influence another cell, either in an inhibitory way or in an excitatory way. The next neuron may be connected to many more neurons, and if the total of excitatory influences is more than the inhibitory influences, it will also "fire", that is, it will create a new action potential at its axon hillock, in this way passing on the information to yet another next neuron, or resulting in an experience or an action. 5. Give the Biological importance of Glial cells. Glial cells, sometimes called neuroglia or simply glia (Greek for "glue"), are non- neuronal cells that maintain homeostasis, form myelin, and provide support and protection for the brain's neurons. In the human brain, there is roughly one glia for every neuron with a ratio of about two neurons for every three glia in the cerebral gray matter. As the Greek name implies, glia are commonly known as the glue of the nervous system; however, this is not fully accurate. The four main functions of glial cells are to surround neurons and hold them in place, to supply nutrients and oxygen to neurons, to insulate one neuron from another, and to destroy pathogens and remove dead neurons. They also modulate neurotransmission. Functions Some glial cells function primarily as the physical support for neurons. Others regulate the internal environment of the brain, especially the fluid surrounding neurons and their synapses, and nutrify neurons. During early embryogenesis, glial cells direct the migration of neurons and produce molecules that modify the growth of axons and dendrites. Recent research indicates that glial cells of the and cerebellum participate in synaptic transmission, regulate the clearance of neurotransmitters from the synaptic cleft, release factors such as ATP, which modulate presynaptic function, and even release neurotransmitters themselves.

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Glial cells are known to be capable of mitosis. By contrast, scientific understanding of whether neurons are permanently post-mitotic, or capable of mitosis, is still developing. In the past, glia had been considered to lack certain features of neurons. For example, glial cells were not believed to have chemical synapses or to release neurotransmitters. They were considered to be the passive bystanders of neural transmission. However, recent studies have shown this to be untrue. For example, astrocytes are crucial in clearance of neurotransmitter from within the synaptic cleft, which provides distinction between arrival of action potentials and prevents toxic build-up of certain neurotransmitters such as glutamate (excitotoxicity). It is also thought that glia play a role in Alzheimer's disease. Furthermore, at least in vitro, astrocytes can release neurotransmitter glutamate in response to certain stimulation. Another unique type of glial cell, the oligodendrocyte precursor cells or OPCs, have very well-defined and functional synapses from at least two major groups of neurons. The only notable differences between neurons and glial cells are neurons' possession of axons and dendrites, and capacity to generate action potentials. Glia ought not to be regarded as 'glue' in the nervous system as the name implies; rather, they are more of a partner to neurons. They are also crucial in the development of the nervous system and in processes such as synaptic plasticity and synaptogenesis. Glia have a role in the regulation of repair of neurons after injury. In the CNS, glia suppresses repair. Glial cells known as astrocytes enlarge and proliferate to form a scar and produce inhibitory molecules that inhibit regrowth of a damaged or severed axon. In the PNS, glial cells known as Schwann cells promote repair. After axonal injury, Schwann cells regress to an earlier developmental state to encourage regrowth of the axon. This difference between PNS and CNS raises hopes for the regeneration of nervous tissue in the CNS. For example a spinal cord may be able to be repaired following injury or severance. Types Microglia Microglia are like specialized macrophages capable of phagocytosis that protect neurons of the central nervous system. They are derived from hematopoietic precursors rather than ectodermal tissue; they are commonly categorized as such because of their supportive role to neurons. These cells comprise approximately 15% of the total cells of the central nervous system. They are found in all regions of the brain and spinal cord. Microglial cells are small relative to macroglial cells, with changing shapes and oblong nuclei. They are mobile within the brain and multiply when the brain is damaged. In the healthy central nervous system, microglia processes constantly sample all aspects of their environment (neurons, macroglia and blood vessels). Astrocytes Astrocytes signal each other using calcium. The gap junctions (also known as electrical synapses) between astrocytes allow the messenger molecule IP3 to diffuse from one astrocyte to another. IP3 activates calcium channels on cellular organelles, releasing calcium into the cytoplasm. This calcium may stimulate the production of more IP3. The net effect is a calcium wave that propagates from cell to cell. Extracellular release of ATP, and consequent activation of purinergic receptors on other astrocytes, may also mediate calcium waves in some cases. It has recently been shown that astrocyte activity is linked to blood flow in the brain, and that this is what is actually being measured in fMRI.

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Ependymal cells Ependymal cells, also named ependymocytes, line the cavities of the CNS and make up the walls of the ventricles. These cells create and secrete cerebrospinal fluid(CSF) and beat their cilia to help circulate that CSF and make up the Blood-CSF barrier. They are also thought to act as neural stem cells. Oligodendrocytes Oligodendrocytes are cells that coat axons in the central nervous system (CNS) with their cell membrane forming a specialized membrane differentiation called myelin, producing the so- called myelin sheath. The myelin sheath provides insulation to the axon that allows electrical signals to propagate more efficiently. Glia retain the ability to undergo cell division in adulthood, whereas most neurons cannot. The view is based on the general deficiency of the mature nervous system in replacing neurons after an injury, such as a stroke or trauma, while very often there is a profound proliferation of glia, or gliosis near or at the site of damage. However, detailed studies found no evidence that 'mature' glia, such as astrocytes or oligodendrocytes, retain the ability of mitosis The amount of brain tissue that is made up of glia cells increases with brain size: the nematode brain contains only a few glia, a fruitfly's brain is 25% glia, that of a mouse, 65%, a human, 90%, and an elephant, 97%.

6. Describe the importance of myelin in the nervous system Myelin is a dielectric (electrically insulating) material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a glial cell. The production of the myelin sheath is called myelination. The production of myelin occurs in the fourteenth week of fetal development, while very little amounts of myelin exist in the brain at the time of birth. During infancy myelination occurs quickly and does not stop until the adolescent stages of life. Because of this rapid myelination, it is essential that children under the age of two receive a diet higher in fats than one of an adult. Schwann cells supply the myelin for peripheral neurons, whereas oligodendrocytes, specifically of the interfascicular type, myelinate the axons of the central nervous system. Myelin is considered a defining characteristic of the (gnathostome) vertebrates, but it has also arisen by parallel evolution in some invertebrates.] Myelin was discovered in 1854 by Rudolf Virchow. Composition of myelin Myelin made by different cell types varies in chemical composition and configuration, but performs the same insulating function. Myelinated axons are white in appearance, hence the "white matter" of the brain. Myelin is about 40 % water; the dry mass of myelin is about 70 - 85 % lipids and about 15 - 30 % proteins. Some of the proteins that make up myelin are myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), and proteolipid protein (PLP). The primary lipid of myelin is a glycolipid called galactocerebroside. The intertwining hydrocarbon chains of sphingomyelin serve to strengthen the myelin sheath. Function of myelin layer The main purpose of a myelin layer (or sheath) is to increase the speed at which impulses propagate along the myelinated fiber. Along unmyelinated fibers, impulses move continuously as waves, but, in myelinated fibers, they hop or "propagate by saltation." Myelin increases electrical

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES resistance across the cell membrane by a factor of 5,000 and decreases capacitance by a factor of 50.Thus, myelination helps prevent the electrical current from leaving the axon. When a peripheral fiber is severed, the myelin sheath provides a track along which regrowth can occur. Unfortunately, the myelin layer does not ensure a perfect regeneration of the nerve fiber. Some regenerated nerve fibers do not find the correct muscle fibers and some damaged motor neurons of the PNS die without re-growth. Damage to the myelin sheath and nerve fiber is often associated with increased functional insufficiency. Unmyelinated fibers and myelinated axons of the mammalian central nervous system do not regenerate.This is mainly due to the fact that the central nervous system is enclosed in bone, thus suffering less trauma than the peripheral nervous system. Some studies reveal that optic nerve fibers can be regenerated in postnatal rats. This optic nerve regeneration depends upon two conditions: axonal die-back has to be prevented with appropriate neurotrophic factors and neurite growth inhibitory components have to be inactivated. This study may lead to further understanding of nerve fiber regeneration in the central nervous system. Demyelination and dysmyelination Demyelination is the loss of the myelin sheath insulating the nerves, and is the hallmark of some neurodegenerative autoimmune diseases, including multiple sclerosis Symptoms of demyelination Demyelination (i.e., the destruction or loss of the myelin sheath) results in diverse symptoms determined by the functions of the affected neurons. It disrupts signals between the brain and other parts of the body; symptoms differ from patient to patient, and have different presentations upon clinical observation and in laboratory studies. 7. Give the importance of Blood Brain Barrier. The blood-brain barrier (BBB) is a separation of circulating blood and cerebrospinal fluid (CSF) in the central nervous system (CNS). It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion of microscopic objects (e.g. bacteria) and large or hydrophilic molecules into the CSF, while allowing the diffusion of small hydrophobic molecules (O2, hormones, CO2). Cells of the barrier actively transport metabolic products such as glucose across the barrier with specific proteins. This "barrier" results from the selectivity of the tight junctions between endothelial cells in CNS vessels that restricts the passage of solutes. At the interface between blood and the brain, endothelial cells are stitched together by these tight junctions, which are composed of smaller subunits, frequently biochemical dimers, that are transmembrane proteins such as occludin, claudins, junctional adhesion molecule (JAM), or ESAM, for example. Each of these transmembrane proteins is anchored into the endothelial cells by another protein complex that includes zo-1 and associated proteins. The blood-brain barrier is composed of high-density cells restricting passage of substances from the bloodstream much more than endothelial cells in capillaries elsewhere in the body. Astrocyte cell projections called astrocytic feet (also known as "glia limitans") surround the endothelial cells of the BBB, providing biochemical support to those cells. The BBB is distinct from the quite similar blood-cerebrospinal fluid barrier, which is a function of the choroidal cells of the choroid plexus, and from the blood-retinal barrier, which can be considered a part of the whole realm of such barriers.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

Several areas of the human brain are not "behind" the BBB. These include the circumventricular organs. Example of this include the roof of the 3rd and 4th ventricles, Capillaries in the pineal gland on the roof of the diencephalon and the pineal gland, which secretes the hormone melatonin "directly into the systemic circulation"[3] as this hormone can pass through the blood-brain barrier. Pathophysiology The blood-brain barrier acts very effectively to protect the brain from many common bacterial infections. Thus, infections of the brain are very rare. However, since antibodies and antibiotics are too large to cross the blood-brain barrier, infections of the brain that do occur are often very serious and difficult to treat. However, the blood-brain barrier becomes more permeable during inflammation, meaning that some antibiotics can get across. Viruses easily bypass the blood-brain barrier by attaching themselves to circulating immune cells. An exception to the bacterial exclusion are the diseases caused by spirochetes, such as Borrelia, which causes Lyme disease, and Treponema pallidum, which causes syphilis. These harmful bacteria seem to breach the blood-brain barrier by physically tunneling through the blood vessel walls. There are also some biochemical poisons that are made up of large molecules that are too big to pass through the blood-brain barrier. This was especially important in primitive or medieval times when people often ate contaminated food. Neurotoxins such as Botulinum in the food might affect peripheral nerves, but the blood-brain barrier can often prevent such toxins from reaching the central nervous system, where they could cause serious or fatal damage. Drugs targeting the brain Overcoming the difficulty of delivering therapeutic agents to specific regions of the brain presents a major challenge to treatment of most brain disorders. In its neuroprotective role, the blood-brain barrier functions to hinder the delivery of many potentially important diagnostic and therapeutic agents to the brain. Therapeutic molecules and genes that might otherwise be effective in diagnosis and therapy do not cross the BBB in adequate amounts. Nanoparticles Nanotechnology may also help in the transfer of drugs across the BBB. Recently, researchers have been trying to build liposomes loaded with nanoparticles to gain access through the BBB. More research is needed to determine which strategies will be most effective and how they can be improved for patients with brain tumors. The potential for using BBB opening to target specific agents to brain tumors has just begun to be explored. Delivering drugs across the blood-brain barrier is one of the most promising applications of nanotechnology in clinical neuroscience. Nanoparticles could potentially carry out multiple tasks in a predefined sequence, which is very important in the delivery of drugs across the blood- brain barrier.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

Diseases involving the blood-brain barrier Meningitis Meningitis is an inflammation of the membranes that surround the brain and spinal cord (these membranes are known as meninges). Meningitis is most commonly caused by infections with various pathogens, examples of which are Streptococcus pneumoniae and Haemophilus influenzae. Epilepsy Epilepsy is a common neurological disease that is characterized by recurrent and sometimes untreatable seizures. Several clinical and experimental data have implicated the failure of blood-brain barrier function in triggering chronic or acute seizures Multiple sclerosis (MS) Multiple sclerosis (MS) is considered to be an auto-immune and neurodegenerative disorder in which the immune system attacks the myelin that protects and electrically insulates the neurons of the central and peripheral nervous systems Alzheimer's Disease Some new evidence indicates that disruption of the blood-brain barrier in Alzheimer's Disease patients allows blood plasma containing amyloid beta (Aβ) to enter the brain where the Aβ adheres preferentially to the surface of astrocytes.

8. Explain the spinal cord The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain (the medulla oblongata specifically). The brain and spinal cord together make up the central nervous system. The spinal cord begins at the Occipital bone and extends down to the space between the first and second lumbar vertebrae; it does not extend the entire length of the vertebral column. It is around 45 cm (18 in) in men and around 43 cm (17 in) long in women. Also, the spinal cord has a varying width, ranging from 1/2 inch thick in the cervical and lumbar regions to 1/4 inch thick in the thoracic area. The enclosing bony vertebral column protects the relatively shorter spinal cord. The spinal cord functions primarily in the transmission of neural signals between the brain and the rest of the body but also contains neural circuits that can independently control numerous reflexes and central pattern generators. The spinal cord has three major functions: A. Serve as a conduit for motor information, which travels down the spinal cord. B. Serve as a conduit for sensory information, which travels up the spinal cord. C. Serve as a center for coordinating certain reflexes The spinal cord is the main pathway for information connecting the brain and peripheral nervous system. The length of the spinal cord is much shorter than the length of the bony spinal column. The human spinal cord extends from the medulla oblongata and continues through the conus medullaris near the first or second lumbar vertebra, terminating in a fibrous extension known as the filum terminale. It is about 45 cm (18 in) long in men and around 43 cm (17 in) in women, ovoid-shaped, and is enlarged in the cervical and lumbar regions. The cervical enlargement, located from C4 to T1, is where sensory input comes from and motor output goes to the arms. The lumbar enlargement, located between T9 and T12, handles sensory input and motor output coming from and going to the legs. You should notice that the name is somewhat misleading. However, this region of the cord does indeed have branches that extend to the lumbar region. The spinal cord is protected by three layers of tissue, called spinal meninges, that

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES surround the canal. The dura mater is the outermost layer, and it forms a tough protective coating. Between the dura mater and the surrounding bone of the vertebrae is a space called the epidural space. The epidural space is filled with adipose tissue, and it contains a network of blood vessels. The arachnoid mater is the middle protective layer The subarachnoid space contains cerebrospinal fluid (CSF). The medical procedure known as a lumbar puncture (or spinal tap) involves use of a needle to withdraw cerebrospinal fluid from the subarachnoid space, usually from the lumbar region of the spine. The pia mater is the innermost protective layer. It is very delicate and it is tightly associated with the surface of the spinal cord. The cord is stabilized within the dura mater by the connecting denticulate ligaments, which extend from the enveloping pia mater laterally between the dorsal and ventral roots. The dural sac ends at the vertebral level of the second sacral vertebra. In cross-section, the peripheral region of the cord contains neuronal white matter tracts containing sensory and motor neurons. Internal to this peripheral region is the gray, butterfly- shaped central region made up of nerve cell bodies. This central region surrounds the central canal, which is an anatomic extension of the spaces in the brain known as the ventricles and, like the ventricles, contains cerebrospinal fluid. The spinal cord has a shape that is compressed dorso-ventrally, giving it an elliptical shape. The cord has grooves in the dorsal and ventral sides. The posterior median sulcus is the groove in the dorsal side, and the anterior median fissure is the groove in the ventral side. Spinal cord segments The human spinal cord is divided into 31 different segments. At every segment, right and left pairs of spinal nerves (mixed; sensory and motor) form. Six to eight motor nerve rootlets branch out of right and left ventro lateral sulci in a very orderly manner. Nerve rootlets combine to form nerve roots. Likewise, sensory nerve rootlets form off right and left dorsal lateral sulci and form sensory nerve roots. The ventral (motor) and dorsal (sensory) roots combine to form spinal nerves (mixed; motor and sensory), one on each side of the spinal cord. Spinal nerves, with the exception of C1 and C2, form inside intervertebral foramen (IVF). Note that at each spinal segment, the border between the central and peripheral nervous system can be observed. Rootlets are a part of the peripheral nervous system. In the upper part of the vertebral column, spinal nerves exit directly from the spinal cord, whereas in the lower part of the vertebral column nerves pass further down the column before exiting. The terminal portion of the spinal cord is called the conus medullaris. The pia mater continues as an extension called the filum terminale, which anchors the spinal cord to the coccyx. The cauda equina (―horse‘s tail‖) is the name for the collection of nerves in the vertebral column that continue to travel through the vertebral column below the conus medullaris. The gray matter, in the center of the cord, is shaped like a butterfly and consists of cell bodies of interneurons and motor neurons. It also consists of neuroglia cells and unmyelinated axons. Projections of the gray matter (the ―wings‖) are called horns. Together, the gray horns and the gray commissure form the ―gray H.‖ The white matter is located outside of the gray matter and consists almost totally of myelinated motor and sensory axons. ―Columns‖ of white matter carry information either up or down the spinal cord. Within the CNS, nerve cell bodies are generally organized into functional clusters, called nuclei. Axons within the CNS are grouped into tracts. There are 33 (some EMS text say 25, counting the sacral as one solid piece) spinal cord

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES nerve segments in a human spinal cord:  8 cervical segments forming 8 pairs of cervical nerves (C1 spinal nerves exit spinal column between occiput and C1 vertebra; C2 nerves exit between posterior arch of C1 vertebra and lamina of C2 vertebra; C3-C8 spinal nerves through IVF above corresponding cervica vertebra, with the exception of C8 pair which exit via IVF between C7 and T1 vertebra)  12 thoracic segments forming 12 pairs of thoracic nerves (exit spinal column through IVF below corresponding vertebra T1-T12)  5 lumbar segments forming 5 pairs of lumbar nerves (exit spinal column through IVF, below corresponding vertebra L1-L5)  5 (or 1) sacral segments forming 5 pairs of sacral nerves (exit spinal column through IVF, below corresponding vertebra S1-S5)  3 coccygeal segments joined up becoming a single segment forming 1 pair of coccygeal nerves (exit spinal column through the sacral hiatus).

9. Briefly describe on Meninges.

The Meninges

The meninges are three layers of protective tissue called the dura mater, arachnoid mater, and pia mater that surround the neuraxis. The meninges of the brain and spinal cord are continuous, being linked through the magnum foramen. Dura Mater The dura mater is the most superior of the meningeal layers. Its name means "hard mother" in Latin and it is tough and inflexible. This tissue forms several structures that separate the cranial cavity into compartments and protect the brain from displacement. The falx cerebri separates the hemispheres of the cerebrum. The falx cerebelli separates the lobes of the cerebellum. The tentorium cerebelli separates the cerebrum from the cerebellum. The dura mater also forms several vein-like sinuses that carry blood (which has already given its supply of oxygen and nutrients to the brain) back to the heart. The superior sagittal sinus runs across the top of the brain in an anterior-posterior direction.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

Other sinuses include the straight sinus, the inferior sinus, and the transverse sinus. The epidural space is a potential space between the dura mater and the skull. If there is hemorrhaging in the brain, blood may collect here. Adults are more likely than children to bleed here as a result of closed head injury. The subdural space is another potential space. It is between the dura mater and the middle layer of the meninges, the arachnoid mater. When bleeding occurs in the cranium, blood may collect here and push down on the lower layers of the meninges. If bleeding continues, brain damage will result from this pressure. Children are especially likely to have bleeding in the subdural space in cases of head injury. Arachnoid Mater The arachnoid or arachnoid mater is the middle layer of the meninges. In some areas, it projects into the sinuses formed by the dura mater. These projections are the arachnoid granulation/arachnoid villi. They transfer cerebrospinal fluid from the ventricles back into the bloodstream. The subarachanoid space lies between the arachnoid and pia mater. It is filled with cerebrospinal fluid. All blood vessels entering the brain, as well as cranial nerves pass through this space. The term arachnoid refers to the spider web like appearance of the blood vessels within the space. Pia Mater The pia mater is the innermost layer of the meninges. Unlike the other layers, this tissue adheres closely to the brain, running down into the sulci and fissures of the cortex. It fuses with the ependyma, the membranous lining of the ventricles to form structures called the choroid plexes which produce cerebrospinal fluid. 10. Explain in detail about the Cerebrospinal fluid Cerebrospinal Fluid Purpose Cerebrospinal fluid is a clear liquid produced within spaces in the brain called ventricles. Like saliva it is a filtrate of blood. It is also found inside the subarachnoid space of the meninges which surrounds both the brain and the spinal chord. In addition, a space inside the spinal chord called the central canal also contains cerebrospinal fluid. It acts as a cushion for the neuraxis, also bringing nutrients to the brain and spinal cord and removing waste from the system. Choroid Plexus All of the ventricles contain choroid plexuses which produce cerebrospinal fluid by allowing certain components of blood to enter the ventricles. The choroid plexuses are formed by the fusion of the pia mater, the most internal layer of the meninges and the ependyma, the lining of the ventricles. The Ventricles These four spaces are filled with cerebrospinal fluid and protect the brain by cushioning it and supporting its weight. The two lateral ventricles extend across a large area of the brain. The anterior horns of these structures are located in the frontal lobes. They extend posteriorly into the parietal lobes and their inferior horns are found in the temporal lobes. The third ventricle lies between the two thalamic bodies. The massa intermedia passes through it and the hypothalamus forms its floor and part of its lateral walls.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

The fourth ventricle is located between the cerebellum and the pons. The four ventricles are connected to one another. The two foramina of Munro, which are also know as the interventricular foramina, link the lateral ventricles to the third ventricle. The Aqueduct of Sylvius which is also called the cerebral aqueduct connects the third and fourth ventricles. The fourth ventricle is connected to the subarachnoid space via two lateral foramina of Luschka and by one medial foramen of Magendie. Subarachnoid Space Although cerebrospinal fluid is manufactured in all of the ventricles, it circulates through the system in a specific pattern, moving from the lateral ventricle to the third, and then from the third to the fourth. From the fourth ventricle, the cerebrospinal fluid passes into the subarachnoid space where it circulates around the outside of the brain and spinal cord and eventually makes its way to the superior sagittal sinus via the arachnoid granulations also called arachnoid villi. In the superior sagittal sinus, the cerebrospinal fluid is reabsorbed into the blood stream. The cerebrospinal fluid of the neuraxis is regenerated several times every twenty-four hours. Endolymph and perilymph, the fluids of the inner ear, are derived from cerebrospinal fluid. Currently, there is no consensus regarding the manner in which cerebrospinal fluid enters the inner ear. Osmosis may be involved. A condition called hydrocephalus occurs when, for some reason, too much cerebrospinal fluid is produced and the ventricles swell, putting pressure on the tissue of the brain. Tumors are one potential cause of an over-production of cerebrospinal fluid. Hydrocephalus should not be confused with hydroencephali. The term hydroencephali literally means "water brain" and refers to a rare birth defect in which the cerebrum is absent and the space where it should be is entirely filled with cerebrospinal fluid. In the past, before CT and MRI technology existed, a technique involving cerebrospinal fluid called pneumoencephalography was used to view the brain. A small amount of cerebrospinal fluid was removed from the ventricular system and replaced with air or some other inert gas. This allowed the examiner to view the ventricles in a scan and make inferences about brain pathology. Tumors and hemorrhages could sometimes be located by examining the shapes and sizes of the ventricles. Because space within the cranium is limited, growths or coagulated blood (hematoma) will displace white and gray matter, pushing them into the ventricular system. Cerebrospinal fluid can be analyzed to make judgments about a person's general health as can blood and saliva .A sample is taken from the spinal cord via a lumbar puncture which is also known as a spinal tap.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

UNIT – II PART – A 1. Define action potential. A momentary change in electrical potential on the surface of a cell, especially of a nerve or muscle cell, that occurs when it is stimulated, resulting in the transmission of an electrical impulse. 2. What is conduction? The speed and strength of a signal being transmitted by nerve cells. Testing these factors can reveal the nature of nerve injury, such as damage to nerve cells or to the protective myelin sheath. Conduction takes place between nerve to nerve or nerve to muscle to bring out response. 3. Define resting potential. The electric potential across a nerve cell membrane before it is stimulated to release the charge. The resting potential for a neuron is between 50 and 100 mV, with the excess of negatively charged ions inside the cell membrane. 4. Give a brief note on neuron. A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous system, which includes the brain, spinal cord, and peripheral ganglia. A number of specialized types of neurons exist: sensory neurons respond to touch, sound, light and numerous other stimuli affecting cells of the sensory organs that then send signals to the spinal cord and brain. 5. Write short notes on nodes of ranvier. Nodes of Ranvier are the gaps (approximately 1 micrometer in length) formed between the myelin sheaths generated by different cells. A myelin sheath is a many-layered coating, largely composed of a fatty substance called myelin, that wraps around the axon of a neuron and very efficiently insulates it. At nodes of Ranvier, the axonal membrane is uninsulated and therefore capable of generating electrical activity. 6. Define Synaptic transmission. Neurotransmission also called synaptic transmission is an electrical movement within synapses caused by a propagation of nerve impulses. As each nerve cell receives neurotransmitter from the presynaptic neuron, or terminal button, to the postsynaptic neuron, or dendrite, of the second neuron, it sends it back out to several neurons, and they do the same, thus creating a wave of energy until the pulse has made its way across an organ or specific area of neurons. 7. Give the importance of Voltage-dependent calcium channels Voltage-dependent calcium channels (VDCC) are a group of voltage-gated ion channels found in excitable cells (e.g., muscle, glial cells, neurons, etc.) with a permeability to the ion Ca2+. At physiologic or resting membrane potential, VDCCs are normally closed. They are activated (i.e., opened) at depolarized membrane potentials and this is the source of the "voltage- dependent" epithet. Activation of particular VDCCs allows Ca2+ entry into the cell, which, depending on the cell type, results in muscular contraction, 8. What is neural coding? Neural coding is a neuroscience-related field concerned with how sensory and other information is represented in the brain by networks of neurons. The main goal of studying neural

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES coding is to characterize the relationship between the stimulus and the individual or ensemble neuronal responses and the relationship among electrical activity of the neurons in the ensemble [1]. It is thought that neurons can encode both digital and analog information 9. Define membrane potential Membrane potential (or transmembrane potential) is the difference in voltage (or electrical potential difference) between the interior and exterior of a cell (Vinterior − Vexterior). All animal cells are surrounded by a plasma membrane composed of a lipid bilayer with many diverse protein assemblages embedded in it. The fluid on both sides of the membrane contains high concentrations of mobile ions, of which sodium (Na+), potassium (K+), chloride (Cl–), and calcium (Ca2+) are the most important. The membrane potential arises from the interaction of ion channels and ion pumps embedded in the membrane, which maintain different ion concentrations on the intracellular and extracellular sides of the membrane. 10. Contrast resting and action potential. Resting potential Action potential This is the electrical state of the cell membrane This is the electrical state of the cell membrane when no signals are being sent. when signals are being sent. The resting potential is always negative. It is The action potential is always positive. It is about -70mV. (The negative sign indicates that about +40mV. (The positive sign indicates that the inside of the cell is negative with respect to the inside of the cell is positive with respect to outside. outside. It is the state of the cell membrane when the It is the state of the cell membrane when the membrane is polarized. membrane is depolarized. During resting membrane potential, potassium During action potential, sodium ions (Na+) can ions (K+) can cross through the membrane cross through the membrane easily while easily while chloride ions (Cl-) and sodium potassium ions (K+) have a more difficult time ions (Na+) have a more difficult time crossing hence there are relatively more crossing hence there are relatively more sodium ions inside the neuron and more sodium ions outside the neuron and more potassium ions outside that neuron. potassium ions inside that neuron.

11. What are neurotransmitters? Neurotransmitters, also known as chemical messengers, are endogenous chemicals that enable neurotransmission. They transmit signals across a chemical synapse, such as a neuromuscular junction, from one neuron (nerve cell) to another "target" neuron, muscle cell, or gland cell. 12. Differentiate chemical and electrical synapse. In chemical synapse, signal transmission In electrical synapse, signal transmission happens through chemical molecules called happens in the form of electrical signals neurotransmitters. without the use of molecules. Signals are modified during the Signals are not modified during the transmission. transmission. Neurotransmitters are released by Electric signal pass via gap junctions. exocytosis and diffused in the synapsis cleft and then are bound to receptors.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

Space between the pre and postsynaptic Space between the pre and postsynaptic ends ends is larger. is very small. Signal transmission happens only into one Signal transmission can happen in both direction. directions. Signal transmission requires energy. So it‘s Signal transmission happens without utilizing an active process. energy. So it‘s a passive process. Signal transmission happens at a moderate Signal transmission is extremely fast. speed.

13. How Na channel helps for conduction of action potential? Na+ channels are responsible for the generation of the rising phase of an action potential, which is the result of a rapid diffusion of Na+ across the axonal membrane. Na+ channels also influence the threshold for action potential generation and the frequency of neuronal firing. 14. What is a depolarized state? When it's time to become active, voltage-gated ion channels, or sodium channels, will open once the membrane charge reaches the threshold voltage, or the minimum charge necessary for a cell to become active. When the threshold voltage is reached, which is typically at -55 mV, the ion channels open in order to allow positive charges to rush inside the cell. This is known as depolarization, which is the process of becoming positively charged. 15. Write a short note on voltage dependent channels. Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in the electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins, regulating their opening and closing. They are found in excitable cells such as neuronal and muscle tissues, allowing a rapid and co- ordinated depolarization in response to triggering voltage change.

PART – B 1. Explain the action potential An action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a stereotyped trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and endocrine cells, as well as in some plant cells. In neurons they play a central role in cell-to-cell communication. In other types of cells, their main function is to activate intracellular processes. In muscle cells, an action potential is the first step in the chain of events leading to contraction. In beta cells of the pancreas, they provoke release of insulin. Action potentials in neurons are also known as "nerve impulses" or "spikes", and the temporal sequence of action potentials generated by a neuron is called its "spike train". A neuron that emits an action potential is often said to "fire". An action potential is a rapid rise and subsequent fall in voltage or membrane potential across a cellular membrane with a characteristic pattern. Sufficient current is required to initiate a voltage response in a cell membrane; if the current is insufficient to depolarize the membrane to the threshold level, an action potential will not fire. Examples of cells that signal via action potentials are neurons and muscle cells.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

Stimulus starts the rapid change in voltage or action potential. In patch-clamp mode, sufficient current must be administered to the cell in order to raise the voltage above the threshold voltage to start membrane depolarization. Depolarization is caused by a rapid rise in membrane potential opening of sodium channels in the cellular membrane, resulting in a large influx of sodium ions. Membrane Repolarization results from rapid sodium channel inactivation as well as a large efflux of potassium ions resulting from activated potassium channels. Hyperpolarization is a lowered membrane potential caused by the efflux of potassium ions and closing of the potassium channels. Resting state is when membrane potential returns to the resting voltage that occurred before the stimulus occurred. In animal cells, there are two primary types of action potentials- voltage-gated sodium channels and voltage-gated calcium channels. Sodium-based action potentials usually last for less than one millisecond, whereas calcium-based action potentials may last for 100 milliseconds or longer. 2. Explain the mechanism of action potential conduction The action potential is conducted along the axon membrane by contiguous conduction and by salitatory conduction. CONTIGUOUS CONDUCTION This is the main process occurring in non-myelinated fibers. The action potential spreads in a fashion similar to graded potentials: The action potential The outside of the cell is more negative than inside the cell The action potential is self limiting Therefore, the area in front of the action potential The outside of the cell is more positive than the inside of the cell Positive charges will move towards the adjacent area of opposite charge This will begin to depolarise this area of the membrane until it reaches threshold potential. Once threshold is reached, the action potential is fired and this is the area of the AP. The area behind the action potential Still in the last stage of the action potential i.e. potassium channels are still open. This is known as the relative refractory period (see below) and the consequence is that the membrane potential can only hyperpolarise (since the permeability to K is still high and the equilibrium potential of K is -90mV).

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

This prevents retrograde conduction of the action potential.

The Refractory Period There are two refractory periods during and after the action potential in which another action potential cannot be generated, no matter how strong the stimulus. The absolute refractory period is when the sodium channels are open (i.e. during the action potential). Once open, Na channels cannot ‗open more‘ to another stimulus. Basically, the action potential is the same for any stimulus. The relative refractory period is when the potassium channels are still open but the sodium channels are closed. Because of the increased permeability to K and its hyperpolarising effect, it is impossible for the membrane to depolarise enough to reach threshold and generate a second AP. The refractory period is also important in ‗deciding‘ the maximum number of action potentials that can occur in a period of time. A stronger stimulus will affect more neurons. Also, different neurons have different properties for conducting different signals. In this way, the AP can travel faster if the fiber is myelinated or if it is a thick fiber (due to a decrease in resistance against the movement of charge. SALTATORY CONDUCTION This is the process of conduction that takes place in myelinated fibers. Myelin acts as an insulator, since ions are not able to cross its non-water barrier. Myelin is formed around the axon in sheaths, in between which are gaps known as Nodes of Ranvier, where the membrane is exposed to the ECF and the voltage gated channels are concentrated. As sodium rushes into the node it creates an electrical force which pushes on the ions already inside the axon. This rapid conduction of electrical signal reaches the next node and creates another action potential, thus refreshing the signal. In this manner, saltatory conduction allows electrical nerve signals to be propagated long distances at high rates without any degradation of the signal. Although the

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES action potential appears to jump along the axon, this phenomenon is actually just the rapid, almost instantaneous, conduction of the signal inside the myelinated portion of the axon.

NB Saltatory conduction also conserves energy (as well as increasing the speed of conduction) because the Na/K pump must only work at the nodal areas.

3. Explain about role of voltage gated ion channels in the nerve conduction

Action potentials are generated by special types of voltage-gated ion channels embedded in a cell's plasma membrane. These channels are shut when the membrane potential is near the (negative) resting potential of the cell, but they rapidly begin to open if the membrane increases to a precisely defined threshold voltage, depolarizing the transmembrane potential. When the channels open, they allow an inward flow of sodium ions, which changes the electrochemical gradient, which in turn produces a further rise in the membrane potential. This then causes more channels to open, producing a greater electric current across the cell membrane, and so on. The process proceeds explosively until all of the available ion channels are open, resulting in a large upswing in the membrane potential. The rapid influx of sodium ions causes the polarity of the plasma membrane to reverse, and the ion channels then rapidly inactivate. As the sodium channels close, sodium ions can no longer enter the neuron, and then they are actively transported back out of the plasma membrane. Potassium channels are then activated, and there is an outward current of potassium ions, returning the electrochemical gradient to the resting state. After an action potential has occurred, there is a transient negative shift, called the afterhyperpolarization.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

4. Write in detail about a Nodes of Ranvier.

Figure: Nodes of Ranvier are microscopic gaps found within myelinated axons. Their function is to speed up propagation of Action potentials along the axon via saltatory conduction. The Node of Ranvier is the 1-2 micrometre gap between the glial cells of the myelin sheath. These glial cells are called Schwann cells, and they help to electrically insulate the neuron. The Nodes of Ranvier are only present when the axon of a neuron is myelinated. Myelination allows for an increased rate of action potential transmission due to action potentials "jumping" between Node of Ranvier, this is called saltatory conduction. The movement of sodium ions to depolarize the membrane can only occur at the Node of Ranvier, as the sodium voltage-gated channels are found only at the nodes of Ranvier.. The Schwann cells of the myelin sheath block the movement of sodium ions elsewhere along the axon. The Nodes of Ranvier are pivotal in the process of saltatory conduction. The Nodes themselves are approximately one micrometre in length apart, and they are the physical gaps between the myelin sheath cells themselves. The action potential can jump from node to node along the axon, causing the transmission speed to reach around 120 metres per second. Each individually myelinated cell is referred to as a Schwann Cell. The myelination sheath produced by the Schwann Cells increases the membrane resistance (Rm), which, along with an increased diameter (D) of the axon will increase the velocity of the action potential. The gaps are rich in ion channels, such as Sodium and Calcium channels, resulting in maximised

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES speed at which ion mediators can be released into tissues and adjacent neurones. This is particularly handy at the synaptic cleft, (the area between a pre and a postsynaptic neurone) because the quicker that sodium ions are released into the cell, the quicker that depolarisation can occur and the faster response is produced as a result of the Action Potential that is caused. Overall, Myelination is a highly specialised property of axons and ensures that impulses travel at sufficiently high speed around the autonomic nervous system so that the body can produce a successful response.

Give detailed note on synapse. In the nervous system, a synapse is a junction that permits a neuron to pass an electrical or chemical signal to another cell (neural or otherwise).

Structure of a typical chemical synapse

Figure: Synapses are essential to neuronal function: neurons are cells that are specialized to pass signals to individual target cells, and synapses are the means by which they do so. At a synapse, the plasma membrane of the signal-passing neuron (the presynaptic neuron) comes into close apposition with the membrane of the target (postsynaptic) cell. Both the presynaptic and postsynaptic sites contain extensive arrays of molecular machinery that link the two membranes together and carry out the signaling process. In many synapses, the presynaptic part is located on an axon, but some presynaptic sites are located on a dendrite or soma. The structure of a typical chemical synapse comes in three parts: The pre-synaptic terminal is usually on the axon. This releases neurotransmitters into the synaptic cleft. The pre-synaptic terminal is the first part of synaptic transmission. The synaptic membrane of the post-synaptic cell is usually on the dendrite of the next neuron. This absorbs neurotransmitters into the post-synaptic neuron (the neuron that is receiving the signal). The post-synaptic cell is the last part of the transmission process. The synaptic cleft is the bit in the middle of the two membranes. This space is filled with an extracellular matrix of proteins that mainly acts to hold the two neurons together. There are two fundamentally different types of synapse: In a chemical synapse, the presynaptic neuron releases a chemical called a neurotransmitter that binds to receptors located in the postsynaptic cell, usually embedded in the plasma membrane.

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Binding of the neurotransmitter to a receptor can affect the postsynaptic cell in a wide variety of ways. In an electrical synapse, the presynaptic and postsynaptic cell membranes are connected by channels that are capable of passing electrical current, causing voltage changes in the presynaptic cell to induce voltage changes in the postsynaptic cell.

5. Give a detailed account on synaptic transmission. Neurotransmission Neurotransmission also called synaptic transmission, is an electrical movement within synapses caused by a propagation of nerve impulses. As each nerve cell receives neurotransmitter from the presynaptic neuron, or terminal button, to the postsynaptic neuron, or dendrite, of the second neuron, it sends it back out to several neurons, and they do the same, thus creating a wave of energy until the pulse has made its way across an organ or specific area of neurons.

Figure: The presynaptic neuron releases neurotransmitter, which activates receptors on the postsynaptic cell. Nerve impulses are essential for the propagation of signals. These signals are sent to and from the central nervous system via efferent and afferent neurons in order to coordinate smooth, skeletal and cardiac muscles, bodily secretions and organ functions critical for the long-term survival of multicellular vertebrate organisms such as mammals. Neurons form networks through which nerve impulses travel. Each neuron receives as many as 15,000 connections from other neurons. Neurons do not touch each other; they have contact points called synapses. A neuron transports its information by way of a nerve impulse. When a nerve impulse arrives at the synapse, it releases neurotransmitters, which influence another cell, either in an inhibitory way or in an excitatory way. The next neuron may be connected to many more neurons, and if the total of excitatory influences is more than the inhibitory influences, it will also "fire", that is, it will create a new action potential at its axon hillock, in this way passing on the information to yet another next neuron, or resulting in an experience or an action. Stages in neurotransmission at the synapse:

Chemical synapse Synthesis of the neurotransmitter. This can take place in the cell body, in the axon, or in the axon terminal.

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Storage of the neurotransmitter in granules or vesicles in the axon terminal. Calcium enters the axon terminal during an action potential, causing release of the neurotransmitter into the synaptic cleft. After its release, the transmitter binds to and activates a receptor in the postsynaptic membrane. Deactivation of the neurotransmitter. The neurotransmitter is either destroyed enzymatically, or taken back into the terminal from which it came, where it can be reused, or degraded and removed.[1] Each neuron is connected with numerous other neurons, receiving numerous impulses from them. Summation is the adding together of these impulses at the axon hillock. If the neuron only gets excitatory impulses, it will also generate an action potential; but if the neuron gets as many inhibitory as excitatory impulses, the inhibition cancels out the excitation and the nerve impulse will stop there. Summation takes place at the axon hillock. Spatial summation means several firings on different places of the neuron, that in themselves are not strong enough to cause a neuron to fire. However, if they fire simultaneously, their combined effects will cause an action potential. Temporal summation means several firings at the same place, that won't cause an action potential if they have a pause in between, but when there are several firings in rapid succession, they will cause the neuron to reach the threshold for excitation.

Convergence and divergence Neurotransmission implies both a convergence and a divergence of information. First one neuron is influenced by many others, resulting in a convergence of input. When the neuron fires, the signal is sent to many other neurons, resulting in a divergence of output. Many other neurons are influenced by this neuron.

Cotransmission Cotransmission is the release of several types of neurotransmitters from a single nerve terminal. Cotransmission allows for more complex effects at postsynaptic receptors, and thus allows for more complex communication to occur between neurons. In modern neuroscience, neurons are often classified by their cotransmitter, for example striatal GABAergic neurons utilize opioid peptides or substance P as their primary cotransmitter. Examples of neuron types releasing two or more neurotransmitters at the same time and include: GABA-glycine co-release. Dopamine-glutamate co-release. Acetylcholine-glutamate co-release. Acetylcholine (ACh) and vasoactive intestinal peptide (VIP) co-release. Acetylcholine (ACh) and calcitonin gene-related peptide (CGRP) co-release. Glutamate and dynorphin co-release (in the hippocampal synapses). NANCs and noradrenaline/acetylcholine/etc.

6. Give the applications nerve coding. Neural coding is a neuroscience-related field concerned with how sensory and other information is represented in the brain by networks of neurons. The main goal of studying neural coding is to characterize the relationship between the stimulus and the individual or ensemble neuronal responses and the relationship among electrical activity of the neurons in the ensemble

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[1]. It is thought that neurons can encode both digital and analog information. Neurons are remarkable among the cells of the body in their ability to propagate signals rapidly over large distances. They do this by generating characteristic electrical pulses called action potentials or, more simply, spikes that can travel down nerve fibers. Sensory neurons change their activities by firing sequences of action potentials in various temporal patterns, with the presence of external sensory stimuli, such as light, sound, taste, smell and touch. It is known that information about the stimulus is encoded in this pattern of action potentials and transmitted into and around the brain. Although action potentials can vary somewhat in duration, amplitude and shape, they are typically treated as identical stereotyped events in neural coding studies. If the brief duration of an action potential (about 1ms) is ignored, an action potential sequence, or spike train, can be characterized simply by a series of all-or-none point events in time. The lengths of interspike intervals (ISIs) between two successive spikes in a spike train often vary, apparently randomly. The study of neural coding involves measuring and characterizing how stimulus attributes, such as light or sound intensity, or motor actions, such as the direction of an arm movement, are represented by neuron action potentials or spikes. In order to describe and analyze neuronal firing, statistical methods and methods of probability theory and stochastic point processes have been widely applied. and decoding The link between stimulus and response can be studied from two opposite points of view. Neural encoding refers to the map from stimulus to response. The main focus is to understand how neurons respond to a wide variety of stimuli, and to accurately construct models that attempt to predict responses to other stimuli. Neural decoding refers to the reverse map, from response to stimulus, and the challenge is to reconstruct a stimulus, or certain aspects of that stimulus, from the spike sequences it evokes. Coding schemes A sequence, or 'train', of spikes may contain information based on different coding schemes. In motor neurons, for example, the strength at which an innervated muscle is flexed depends solely on the 'firing rate', the average number of spikes per unit time (a 'rate code'). At the other end, a complex 'temporal code' is based on the precise timing of single spikes. They may be locked to an external stimulus such as in the auditory system or be generated intrinsically by the neural circuitry. Whether neurons use rate coding or temporal coding is a topic of intense debate within the neuroscience community, even though there is no clear definition of what these terms mean. Rate coding Rate coding is a traditional coding scheme, assuming that most, if not all, information about the stimulus is contained in the firing rate of the neuron. Because the sequence of action potentials generated by a given stimulus varies from trial to trial, neuronal responses are typically treated statistically or probabilistically. They may be characterized by firing rates, rather than as specific spike sequences. In most sensory systems, the firing rate increases, generally non-linearly, with increasing stimulus intensity. Any information possibly encoded in the temporal structure of the spike train is ignored. Consequently, rate coding is inefficient but highly robust with respect to the ISI 'noise'. The concept of firing rates has been successfully applied during the last 80 years. It dates back to the pioneering work of ED Adrian who showed that the firing rate of stretch receptor

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES neurons in the muscles is related to the force applied to the muscle. In the following decades, measurement of firing rates became a standard tool for describing the properties of all types of sensory or cortical neurons, partly due to the relative ease of measuring rates experimentally. However, this approach neglects all the information possibly contained in the exact timing of the spikes. During recent years, more and more experimental evidences have suggested that a straightforward firing rate concept based on temporal averaging may be too simplistic to describe brain activity. During rate coding, precisely calculating firing rate is very important. In fact, the term ―firing rate‖ has a few different definitions, which refer to different averaging procedures, such as an average over time or an average over several repetitions of experiment. Spike-count rate The Spike-count rate, also referred to as temporal average, is obtained by counting the number of spikes that appear during a trial and dividing by the duration of trial. The length T of the time window is set by experimenter and depends on the type of neuron recorded from and the stimulus. In practice, to get sensible averages, several spikes should occur within the time window. Typical values are T = 100 ms or T = 500 ms, but the duration may also be longer or shorter. The spike-count rate can be determined from a single trial, but at the expense of losing all temporal resolution about variations in neural response during the course of the trial. Temporal averaging can work well in cases where the stimulus is constant or slowly varying and does not require a fast reaction of the organism - and this is the situation usually encountered in experimental protocols. Real-world input, however, is hardly stationary, but often changing on a fast time scale. For example, even when viewing a static image, humans perform saccades, rapid changes of the direction of gaze. The image projected onto the retinal photoreceptors changes therefore every few hundred milliseconds. Despite its shortcomings, the concept of a spike-count rate code is widely used not only in experiments, but also in models of neural networks. It has led to the idea that a neuron transforms information about a single input variable (the stimulus strength) into a single continuous output variable (the firing rate). Time-dependent firing rate The time-dependent firing rate is defined as the average number of spikes (averaged over trials) appearing during a short interval between times t and t+Δt, divided by the duration of the interval. It works for stationary as well as for time-dependent stimuli. To experimentally measure the time-dependent firing rate, the experimenter records from a neuron while stimulating with some input sequence. The same stimulation sequence is repeated several times and the neuronal response is reported in a Peri-Stimulus-Time Histogram (PSTH). The time t is measured with respect to the start of the stimulation sequence. The Δt must be large enough (typically in the range of one or a few milliseconds) so there are sufficient number of spikes within the interval to obtain a reliable estimate of the average. The number of occurrences of spikes nK(t;t+Δt) summed over all repetitions of the experiment divided by the number K of repetitions is a measure of the typical activity of the neuron between time t and t+Δt. A further division by the interval length Δt yields time-dependent firing rate r(t) of the neuron, which is equivalent to the spike density of PSTH. For sufficiently small Δt, r(t)Δt is the average number of spikes occurring between times t and t+Δt over multiple trials. If Δt is small, there will never be more than one spike within the

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES interval between t and t+Δt on any given trial. This means that r(t)Δt is also the fraction of trials on which a spike occurred between those times. Equivalently, r(t)Δt is the probability that a spike occurs during this time interval. As an experimental procedure, the time-dependent firing rate measure is a useful method to evaluate neuronal activity, in particular in the case of time-dependent stimuli. The obvious problem with this approach is that it can not be the coding scheme used by neurons in the brain. Neurons can not wait for the stimuli to repeatedly present in an exactly same manner before generating response. Nevertheless, the experimental time-dependent firing rate measure can make sense, if there are large populations of independent neurons that receive the same stimulus. Instead of recording from a population of N neurons in a single run, it is experimentally easier to record from a single neuron and average over N repeated runs. Thus, the time-dependent firing rate coding relies on the implicit assumption that there are always populations of neurons. Temporal coding When precise spike timing or high-frequency firing-rate fluctuations are found to carry information, the neural code is often identified as a temporal code [8]. A number of studies have found that the temporal resolution of the neural code is on a millisecond time scale, indicating that precise spike timing is a significant element in neural coding [9]. Temporal codes employ those features of the spiking activity that cannot be described by the firing rate. For example, time to first spike after the stimulus onset, characteristics based on the second and higher statistical moments of the ISI probability distribution, spike randomness, or precisely timed groups of spikes (temporal patterns) are candidates for temporal codes . As there is no absolute time reference in the nervous system, the information is carried either in terms of the relative timing of spikes in a population of neurons or with respect to an ongoing brain oscillation. The temporal structure of a spike train or firing rate evoked by a stimulus is determined both by the dynamics of the stimulus and by the nature of the neural encoding process. Stimuli that change rapidly tend to generate precisely timed spikes and rapidly changing firing rates no matter what neural coding strategy is being used. Temporal coding refers to temporal precision in the response that does not arise solely from the dynamics of the stimulus, but that nevertheless relates to properties of the stimulus. The interplay between stimulus and encoding dynamics makes the identification of a temporal code difficult. The issue of temporal coding is distinct and independent from the issue of independent- spike coding. If each spike is independent of all the other spikes in the train, the temporal character of the neural code is determined by the behavior of time-dependent firing rate r(t). If r(t) varies slowly with time, the code is typically called a rate code, and if it varies rapidly, the code is called temporal. Phase-of-firing code is a recent type of code which is often categorized as a temporal code. It takes into account a time label for each spike according to a time reference based on phase of local ongoing oscillations at low frequencies.[11] Population coding Population coding is a method to represent stimuli by using the joint activities of a number of neurons. In population coding, each neuron has a distribution of responses over some set of inputs, and the responses of many neurons may be combined to determine some value about the inputs.

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From the theoretical point of view, population coding is one of a few mathematically well-formulated problems in neuroscience. It grasps the essential features of neural coding and yet, is simple enough for theoretic analysis. Experimental studies have revealed that this coding paradigm is widely used in the sensor and motor areas of the brain. For example, in the visual area medial temporal (MT), neurons are tuned to the moving direction. In response to an object moving in a particular direction, many neurons in MT fire, with a noise-corrupted and bell- shaped activity pattern across the population. The moving direction of the object is retrieved from the population activity, to be immune from the fluctuation existing in a single neuron‘s signal. Population coding has a number of advantages, including reduction of uncertainty due to neuronal variability and the ability to represent a number of different stimulus attributes simultaneously. Population coding is also much faster than rate coding and can reflect changes in the stimulus conditions nearly instantaneously [14]. Individual neurons in such a population typically have different but overlapping selectivities, so that many neurons, but not necessarily all, respond to a given stimulus. Position coding A typical population code involves neurons with a Gaussian tuning curve whose means vary linearly with the stimulus intensity, meaning that the neuron responds most strongly (in terms of spikes per second) to a stimulus near the mean. The actual intensity could be recovered as the stimulus level corresponding to the mean of the neuron with the greatest response. However, the noise inherent in neural responses means that a maximum likelihood estimation function is more accurate. This type of code is used to encode continuous variables such as joint position, eye position, color, or sound frequency. Any individual neuron is too noisy to faithfully encode the variable using rate coding, but an entire population ensures greater fidelity and precision.

7. Explain the chemical transmission Signaling in chemical synapses

The process begins with a wave of electrochemical excitation called an action potential traveling along the membrane of the presynaptic cell, until it reaches the synapse. The electrical depolarization of the membrane at the synapse causes channels to open that are permeable to calcium ions. Calcium ions flow through the presynaptic membrane, rapidly increasing the calcium concentration in the interior. The high calcium concentration activates a set of calcium-sensitive proteins attached to vesicles that contain a neurotransmitter chemical. These proteins change shape, causing the membranes of some "docked" vesicles to fuse with the membrane of the presynaptic cell, thereby opening the vesicles and dumping their neurotransmitter contents into the synaptic cleft, the narrow space between the membranes of the pre- and post-synaptic cells. The neurotransmitter diffuses within the cleft. Some of it escapes, but some of it binds to chemical receptor molecules located on the membrane of the postsynaptic cell. The binding of neurotransmitter causes the receptor molecule to be activated in some way. Several types of activation are possible, as described in more detail below. In any case, this is the

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES key step by which the synaptic process affects the behavior of the postsynaptic cell. Due to thermal shaking, neurotransmitter molecules eventually break loose from the receptors and drift away. The neurotransmitter is either reabsorbed by the presynaptic cell, and then repackaged for future release, or else it is broken down metabolically. 5 Steps to Chemical Synaptic Transmission The electrical signal cannot ―jump‖ over that gap. Instead, at the point of synaptic junction between two neurons, the electrical signal is ―translated‖ into a chemical message (the neurotransmitter) by the presynaptic neuron (at the presynaptic terminal) – Step 1 & 2. That chemical diffuses (―swims‖) across the synaptic cleft until it reaches the other neuron – Step 2 & 3. The other neuron then ―translates‖ the chemical signal back into an electrical one – Step 3 & 4. The chemical message is degraded – Step 5. This ―new‖ electrical message can now travel down the neuron until it reaches a new synaptic junction.

There are two general classes of neurotransmitters: large neuropeptides or smaller amines/amino acids which are synthesized differently. Step 1 – Neurotransmitter Synthesis There are two general classes of neurotransmitters: large neuropeptides or smaller amines/amino acids. The large peptides are synthesized in the cell body of the neuron and are transported to the synaptic terminal through the axon. The smaller amines/amino acids can generally be synthesized at the presynaptic terminal itself. Step 2 & 3- Neurotransmitter Packaging and Release Once the neurotransmitters are synthesized, they need to be put into ―small groups‖ ready to be ―launched‖ across the synaptic cleft. In neurobiological terms, we say that the neurotransmitters need to be packaged into vesicles. Neurotransmitters are packaged into vesicles and are released into the synaptic cleft when they receive an order from Ca 2+ ions to do so The small groups of neurotransmitters are released into the synaptic cleft when they receive an order from Ca 2+ ions to do so. When the electrical signal reaches the presynaptic terminal, it opens some channels in the membrane (these are called voltage gated Ca 2+ channels). Once these channels are open, calcium ions from the surrounding extracellular environment rush into the presynaptic terminal. As the calcium ions encounter the vesicles, the membrane of the vesicles fuse with the membrane of the presynaptic terminal, right at the synaptic cleft. As the vesicles fuse with the membrane, the neurotransmitters are ―expelled‖ into the synaptic cleft.

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Step 4 – Neurotransmitter Binding

The membrane of the postsynaptic neuron contains receptors that control how a neurotransmitter can be translated into an electrical signal The neurotransmitters can now ―swim‖ (diffuse) through the synaptic cleft, until they reach the postsynaptic neuron. The membrane of the postsynaptic neuron contains a few channels (receptors) that control how a neurotransmitter can be translated into an electrical signal. Step 5 – Stopping the Chemical Signal Once the chemical / neurotransmitter signal has been translated into an electrical signal, the postsynaptic receptors need to be ―cleared‖ very quickly so that they can receive new transmitters from new signals (otherwise you‘d end up with neurotransmitter traffic worse than any traffic you‘ve ever experienced on the freeway!). Some neurotransmitters will be degraded, some will be transported back to the presynaptic terminal to be recycled, and sometimes they are ―absorbed‖ by the postsynaptic terminal…

Receptors are cleared and neurotransmitters may (1) be recycled back to the presynaptic terminal, (2) be degraded, and (3) some

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UNIT – III PART – A 1. Define synapse. In the nervous system, a synapse is a junction that permits a neuron to pass an electrical or chemical signal to another cell. Synapses are essential to neuronal function: neurons are cells that are specialized to pass signals to individual target cells, and synapses are the means by which they do so. At a synapse, the plasma membrane of the signal-passing neuron (the presynaptic neuron) comes into close apposition with the membrane of the target (postsynaptic) cell. In many synapses, the presynaptic part is located on an axon, but some presynaptic sites are located on a dendrite or soma. 2. Name the types of Synapses. There are two fundamentally different types of synapse:  Chemical synapse- the presynaptic neuron releases a chemical called a neurotransmitter that binds to receptors located in the postsynaptic cell, usually embedded in the plasma membrane. Binding of the neurotransmitter to a receptor can affect the postsynaptic cell in a wide variety of ways.  Electrical synapse- the presynaptic and postsynaptic cell membranes are connected by channels that are capable of passing electrical current, causing voltage changes in the presynaptic cell to induce voltage changes in the postsynaptic cell. 3. Differentiate chemical and electrical synapse

In chemical synapse, signal transmission In electrical synapse, signal transmission happens through chemical molecules called happens in the form of electrical signals neurotransmitters. without the use of molecules. Signals are modified during the transmission. Signals are not modified during the transmission. Neurotransmitters are released by Electric signal pass via gap junctions. exocytosis and diffused in the synapsis cleft and then are bound to receptors. Space between the pre and postsynaptic Space between the pre and postsynaptic ends is larger. ends is very small. Signal transmission happens only into one Signal transmission can happen in both direction. directions. Signal transmission requires energy. So it‘s Signal transmission happens without an active process. utilizing energy. So it‘s a passive process. Signal transmission happens at a moderate Signal transmission is extremely fast. speed.

4. Define neurotransmitters  Neurotransmitters are endogenous chemicals that enable neurotransmission.

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 It is a type of chemical messenger which transmits signals across a chemical synapse, such as a neuromuscular junction, from one neuron (nerve cell) to another "target" neuron, muscle cell, or gland cell. 5. What is slow neurotransmission?  Their receptors are called as metabotropic receptors.  Slower-acting neurotransmitters act by binding to proteins that are sometimes called G- protein-coupled receptors (GPCRs).  These receptors do not form ion channels upon activation. The conformational change produced when a neurotransmitter binds to a GPCR causes the G-protein to become activated. Once it becomes activated, the protein subunits dissociate and diffuse along the intracellular membrane surface to open or close an ion channel or to activate or inhibit an enzyme that will, in turn, produce a molecule called a second messenger.  Second messengers include cyclic AMP , cyclic GMP , and calcium ions and phosphatidyl inositol.  They serve to activate enzymes known as protein kinases. Protein kinases in turn act to phosphorylate a variety of proteins within a cell, possibly including ion channels. 6. What is Fast neurotransmission?  Some neurotransmitters are referred to as fast-acting since their cellular effects occur milliseconds after the neurotransmitter binds to its receptor.  These neurotransmitters exert direct control of ion channels by inducing a conformational change in the receptor, creating a passage through which ions can flow.  These receptors (ionotropic receptors) are often called ligand -gated ion channels since the channel opens only when the ligand is bound correctly. When the channel opens, it allows for ions to pass through from their side of highest concentration to their side of lowest concentration.  The net result is depolarization if there is a net influx of positively charged ions or hyperpolarization if there is a net inward movement of negatively charged ions.

7. Differentiate inhibitory and excitatory neuro transmitter  Excitatory neurotransmitters: These types of neurotransmitters have excitatory effects on the neuron, meaning they increase the likelihood that the neuron will fire an action potential. Some of the major excitatory neurotransmitters include epinephrine and norepinephrine.  Inhibitory neurotransmitters: These types of neurotransmitters have inhibitory effects on the neuron; they decrease the likelihood that the neuron will fire an action potential. Some of the major inhibitory neurotransmitters include serotonin and gamma- aminobutyric acid (GABA).

8. Write short notes on neuritis. Neuritis is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of or trauma to the nerve or the side-effects of systemic illness. The four cardinal patterns of peripheral neuropathy are polyneuropathy, mononeuropathy, mononeuritis multiplex and autonomic neuropathy. The most common form is (symmetrical) peripheral polyneuropathy, which mainly affects the

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES feet and legs. 9. What is the difference between neurotransmitters and neuromodulators? Neurotransmitters  A neurotransmitter is one of several substances released by the nerve ending of a neuron that is used to communicate with the adjacent neuron.eg., Chemicals like Serotonin, Acetylcholine, Dopamine, GABA, Glycine, and Norepinephrine.  They are released by the presynaptic neuron and either excite or inhibit the post synaptic neuron. They are quickly degraded in the synaptic cleft or taken up by the presynaptic neuron to limit the amount of time they are in the synaptic cleft. Neuromodulators  They are released by the nerve endings and have their effect sometimes quite far from the neuron from which they were released.  They are not rapidly degraded or taken up, so the amount of time for their activity is not limited as in neurotransmitters.  They can either dampen or enhance the excitability of their effector neurons.  Examples of neuromodulators are opioid peptides such as enkephalins, endorphins, dynorphins. 10. Describe the role of para thyroid hormones on neuronal functions. Parathyroid gland There are four parathyroid glands. They are small, light-colored lumps that stick out from the surface of the thyroid gland. All four glands are located on the thyroid gland. The most important functions is  to regulate the body's calcium and phosphorus levels.  to secrete parathyroid hormone, which causes the release of the calcium present in bone to extracellular fluid. PTH or Parathyroid Hormone is secreted from these four glands. It is released directly into the bloodstream and travels to its target cells which are often quite far away. It then binds to a structure called a receptor, that is found either inside or on the surface of the target cells. Calcium provides the electrical system for our nerves, and muscles, allowing the nerves to conduct electricity and the muscles to contract.

11. Explain the role of testosterone on Brain  As testosterone affects the entire body (often by enlarging; men have bigger hearts, lungs, liver, etc.), the brain is also affected by this "sexual" differentiation; the enzymearomatase converts testosterone into estradiol that is responsible for masculinization of the brain in male mice..  Testosterone affects (the ability to focus on a particular object or task), memory and spatial ability in humans.  Low testosterone levels may be a factor in cognitive decline and may possibly increase the risk of Alzheimer‘s .  Testosterone levels gradually decrease with age.  Other factors that can affect testosterone levels include exercise (resistance training increases levels of the hormone) and nutrition – Vitamin A deficiency lowers testosterone, while supplementation with zinc and vitamin D can increase testosterone.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

Weight loss can increase testosterone levels. Ingestion of licorice can decrease testosterone production, more so in females than males. 12. Describe the role of estrogen on mental health Mental health Estrogen is considered to play a significant role in women‘s mental health. Sudden estrogen withdrawal, fluctuating estrogen, and periods of sustained oestrogen low levels correlates with significant mood lowering. Clinical recovery from postpartum, perimenopause, and postmenopause depression has been shown to be effective after levels of oestrogen were stabilized and/or restored. Low oestrogen levels in male lab mice may be one cause of obsessive–compulsive disorder (OCD). When oestrogen levels were raised through the increased activity of the enzyme aromatase in male lab mice, OCD rituals were dramatically decreased. Hypothalamic protein levels in the gene COMT are enhanced by increasing oestrogen levels which is believed to return mice that displayed OCD rituals to normal activity. Aromatase deficiency is ultimately suspected which is involved in the synthesis of oestrogen in humans and has therapeutic implications in humans having obsessive-compulsive disorder. 13. Write short notes on progesterone on nervous system. Nervous system Progesterone, like pregnenolone and dehydroepiandrosterone, belongs to the group of neurosteroids. It can be synthesized within the central nervous system and also serves as a precursor to another major neurosteroid, allopregnanolone. Neurosteroids affect synaptic functioning, are neuroprotective, and affect myelination. They are investigated for their potential to improve memory and cognitive ability. Progesterone affects regulation of apoptotic genes. Its effect as a neurosteroid works predominantly through the GSK-3 beta pathway, as an inhibitor. (Other GSK-3 beta inhibitors include bipolar mood stabilizers, lithium and valproic acid.) 14. Explain the role of adrenaline on nervous system. The major physiologic triggers of adrenaline release center upon stresses such as physical threat, excitement, noise, bright lights, and high ambient temperature. All of these stimuli are processed in the central nervous system. Adrenocorticotropic hormone (ACTH) and the sympathetic nervous system stimulate the synthesis of adrenaline precursors by enhancing the activity of tyrosine hydroxylase and dopamine-β-hydroxylase, two key enzymes involved in catecholamine synthesis. ACTH also stimulates the adrenal cortex to release cortisol, which increases the expression of PNMT in chromaffin cells, enhancing adrenaline synthesis. This is most often done in response to stress. The sympathetic nervous system, acting via splanchnic nerves to the adrenal medulla, stimulates the release of adrenaline. Acetylcholine released by preganglionic sympathetic fibers of these nerves acts on nicotinic acetylcholine receptors, causing cell depolarization and an influx of calcium through voltage-gated calcium channels. Calcium triggers the exocytosis of chromaffin granules and thus the release of adrenaline (and noradrenaline) into the bloodstream. Adrenaline (as with noradrenaline) does exert negative feedback to down-regulate its own synthesis at the presynaptic alpha-2 adrenergic receptor. Abnormally elevated levels of adrenaline can occur in a variety of conditions, such as surreptitious epinephrine administration,

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES pheochromocytoma, and other tumors of the sympathetic ganglia. Its action is terminated with re-uptake into nerve terminal endings, some minute dilution, and metabolism by monoamine oxidase and catechol-o-methyl transferase. 15. Give examples for beta 1 agonist and their clinical utility. (AU nov.2016)  Beta adrenergic agonists or beta agonists are medications that relax muscles of the airways, which widen the airways and result in easier breathing. Eg., denopamine, dobutamine, etc.  Beta adrenoreceptor agonist ligands mimic the action of epinephrine and norepinephrine signaling in the heart, lungs, and smooth muscle tissue, with epinephrine expressing the highest affinity.  They are used for trearing Asthma, Chronic obstructive pulmonary disease (COPD), Heart failure, Allergic reactions 16. Classify muscarinic receptors and give their functions along with examples of specific agonists. (AU nov.2016) Muscarinic receptors are characterised through their interaction with muscarine, a water- soluble toxin derived from the mushroom Amanita muscaria that causes substantial activation of the peripheral sympathetic nervous system through its binding to muscarinic AChRs, resulting in convulsions and even death. The muscarinic AChRs occur primarily in the CNS, and are part of a large family of G- protein-coupled receptors, which use an intracellular secondary messenger system involving an increase of intracellular calcium to transmit signals inside cells. Binding of acetylcholine to a muscarinic AChR causes a conformational change in the receptor that is responsible for its association with and activation of an intracellular G protein, the latter converting GTP to GDP in order to become activated and dissociate from the receptor. The activated G protein can then act as an enzyme to catalyse downstream intracellular events. Muscarinic receptors are involved in a large number of physiological functions including heart rate and force, contraction of smooth muscles and the release of neurotransmitters. There are five subtypes of muscarinic AChRs based on pharmacological activity: M1- M5. All five are found in the CNS, while M1-M4 are also found in various tissues: M1 AChRs are common in secretory glands; M2 AChRs are found in cardiac tissue; M3 AChRs are found in smooth muscles and in secretion glands. M1, M3 and M5 receptors cause the activation of phospholipase C, generating two secondary messengers (IP3 and DAG) eventually leading to an intracellular increase of calcium, while M2 and M4 inhibit adenylate cyclase, thereby decreasing the production of the second messenger cAMP. The activation of the M2 receptor in the heart is important for closing calcium channels in order to reduce the force and rate of contraction. Eg., Bethanechol- used tot trear non obstructive urinary retention 17. How is neurotransmitter removed from synaptic cleft? (AU Nov.2017)  It can be destroyed by enzymes in the synaptic cleft  It can be taken back into the presynaptic axon terminal by a process called reuptake.

18. What are neurites? (AU Nov.2017)  A neurite or neuronal process refers to any projection from the cell body of a neuron.  This projection can be either an axon or a dendrite.

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

PART – B 1. Explain the process of synaptic transmission In the nervous system, a synapse is a junction that permits a neuron to pass an electrical or chemical signal to another cell (neural or otherwise). Synapses are essential to neuronal function: neurons are cells that are specialized to pass signals to individual target cells, and synapses are the means by which they do so. At a synapse, the plasma membrane of the signal-passing neuron (the presynaptic neuron) comes into close apposition with the membrane of the target (postsynaptic) cell. Both the presynaptic and postsynaptic sites contain extensive arrays of molecular machinery that link the two membranes together and carry out the signaling process. In many synapses, the presynaptic part is located on an axon, but some presynaptic sites are located on a dendrite or soma. There are two fundamentally different types of synapse: In a chemical synapse, the presynaptic neuron releases a chemical called a neurotransmitter that binds to receptors located in the postsynaptic cell, usually embedded in the plasma membrane. Binding of the neurotransmitter to a receptor can affect the postsynaptic cell in a wide variety of ways. In an electrical synapse, the presynaptic and postsynaptic cell membranes are connected by channels that are capable of passing electrical current, causing voltage changes in the presynaptic cell to induce voltage changes in the postsynaptic cell.

Figure: The presynaptic neuron releases neurotransmitter, which activates receptors on the postsynaptic cell. Neurotransmission, also called synaptic transmission, is an electrical movement within synapses caused by a propagation of nerve impulses. As each nerve cell receives neurotransmitter from the presynaptic neuron, or terminal button, to the postsynaptic neuron, or dendrite, of the second neuron, it sends it back out to several neurons, and they do the same, thus creating a wave of energy until the pulse has made its way across an organ or specific area of neurons. Nerve impulses are essential for the propagation of signals. These signals are sent to and from the central nervous system via efferent and afferent neurons in order to coordinate smooth, skeletal and cardiac muscles, bodily secretions and organ functions critical for the long-term survival of multicellular vertebrate organisms such as mammals. When a nerve impulse arrives at the synapse, it releases neurotransmitters, which influence another cell, either in an inhibitory way or in an excitatory way. The next neuron may be connected to many more neurons, and if the total of excitatory influences is more than the

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES inhibitory influences, it will also "fire", that is, it will create a new action potential at its axon hillock, in this way passing on the information to yet another next neuron, or resulting in an experience or an action. Stages in neurotransmission at the synapse. Chemical synapse  Synthesis of the neurotransmitter. This can take place in the cell body, in the axon, or in the axon terminal.  Storage of the neurotransmitter in storage granules or vesicles in the axon terminal.  Calcium enters the axon terminal during an action potential, causing release of the neurotransmitter into the synaptic cleft.  After its release, the transmitter binds to and activates a receptor in the postsynaptic membrane.  Deactivation of the neurotransmitter. The neurotransmitter is either destroyed enzymatically, or taken back into the terminal from which it came, where it can be reused, or degraded and removed. Summation Each neuron is connected with numerous other neurons, receiving numerous impulses from them. Summation is the adding together of these impulses at the axon hillock. If the neuron only gets excitatory impulses, it will also generate an action potential; but if the neuron gets as many inhibitory as excitatory impulses, the inhibition cancels out the excitation and the nerve impulse will stop there. Summation takes place at the axon hillock.  Spatial summation means several firings on different places of the neuron if they fire simultaneously, their combined effects will cause an action potential.  Temporal summation means several firings at the same place, that won't cause an action potential if they have a pause in between, but when there are several firings in rapid succession, they will cause the neuron to reach the threshold for excitation. 2. Explain the role of neurotransmitteres with examples Neurotransmitters are stored in a synapse in synaptic vesicles, clustered beneath the membrane in the axon terminal located at the presynaptic side of the synapse. Neurotransmitters are released into and diffused across the synaptic cleft, where they bind to specific receptors in the membrane on the postsynaptic side of the synapse. Most neurotransmitters are about the size of a single amino acid; however, some neurotransmitters may be the size of larger proteins or peptides. A released neurotransmitter is typically available in the synaptic cleft for a short time before it is metabolized by enzymes, pulled back into the presynaptic neuron through reuptake, or bound to a postsynaptic receptor. In response to a threshold action potential or graded electrical potential, a neurotransmitter is released at the presynaptic terminal. Low level "baseline" release also occurs without electrical stimulation. The released neurotransmitter may then move across the synapse to be detected by and bind with receptors in the postsynaptic neuron. Binding of neurotransmitters may influence the postsynaptic neuron in either an inhibitory or excitatory way. This neuron may be connected to many more neurons, and if the total of excitatory influences are greater than those of inhibitory influences, the neuron will also "fire". Ultimately it will create a new action potential at its axon hillock to release neurotransmitters and pass on the information to yet another

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES neighboring neuron Few examples of important neurotransmitter actions:  Glutamate is used at the great majority of fast excitatory synapses in the brain and spinal cord. It is also used at most synapses that are "modifiable", i.e. capable of increasing or decreasing in strength. Modifiable synapses are thought to be the main memory-storage elements in the brain. Excessive glutamate release can overstimulate the brain and lead to excitotoxicity causing cell death resulting in seizures or strokes. Excitotoxicity has been implicated in certain chronic diseases including ischemic stroke, epilepsy, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington disease, and Parkinson's disease.  GABA is used at the great majority of fast inhibitory synapses in virtually every part of the brain. Many sedative/tranquilizing drugs act by enhancing the effects of GABA. Correspondingly, glycine is the inhibitory transmitter in the spinal cord.  Acetylcholine was the first neurotransmitter discovered in the peripheral and central nervous systems. It activates skeletal muscles in the somatic nervous system and may either excite or inhibit internal organs in the autonomic system. It is distinguished as the transmitter at the neuromuscular junction connecting motor nerves to muscles Acetylcholine also operates in many regions of the brain, but using different types of receptors, including nicotinic and muscarinic receptors.  Dopamine has a number of important functions in the brain; this includes regulation of motor behavior, pleasures related to motivation and also emotional arousal. It plays a critical role in the reward system; Parkinson's disease has been linked to low levels of dopamine and schizophrenia has been linked to high levels of dopamine.  Serotonin is a monoamine neurotransmitter. Most is produced by and found in the intestine (approximately 90%), and the remainder in central nervous system neurons. It functions to regulate appetite, sleep, memory and learning, temperature, mood, behaviour, muscle contraction, and function of the cardiovascular system and endocrine system. 3. Describe the fast and slow neurotransmission

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

Ligand-activated ion channels The first class of neurotransmitter receptors are ligand-activated ion channels, also known as ionotropic receptors. They undergo a change in shape when neurotransmitter binds, causing the channel to open. This may have either an excitatory or an inhibitory effect, depending on the ions that can pass through the channel and their concentrations inside and outside the cell. Ligand-activated ion channels are large protein complexes. They have certain regions that are binding sites for the neurotransmitter, as well as membrane-spanning segments that make up the channel. When neurotransmitter binds to the channel, it opens and cations flow down their concentration gradient and into the cell, causing a depolarization. Ligand-activated ion channels typically produce very quick physiological responses. Current starts to flow (ions start to cross the membrane) within tens of microseconds of neurotransmitter binding, and the current stops as soon as the neurotransmitter is no longer bound to its receptors. In most cases, the neurotransmitter is removed from the synapse very rapidly, thanks to enzymes that break it down or neighboring cells that take it up. Eg., Ligand-activated ion channels include the nicotinic acetylcholine receptors, many of the receptors for the amino acid neurotransmitters glutamate, glycine, and GABA. Metabotropic receptors Activation of the second class of neurotransmitter receptors only affects ion channel opening and closing indirectly. In this case, the protein to which the neurotransmitter binds—the neurotransmitter receptor—is not an ion channel. Signaling through these metabotropic receptors depends on the activation of several molecules inside the cell and often involves a second messenger pathway. Because it involves more steps, signaling through metabotropic receptors is much slower than signaling through ligand-activated ion channels. The ligand binds to the receptor, which triggers a signaling cascade inside the cell. The signaling

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

cascade causes the ion channel to open, allowing cations to flow down their concentration gradient and into the cell, resulting in a depolarization. Some metabotropic receptors have excitatory effects when they're activated (make the cell more likely to fire an action potential), while others have inhibitory effects. Often, these effects occur because the metabotropic receptor triggers a signaling pathway that opens or closes an ion channel. Alternatively, a neurotransmitter that binds to a metabotropic receptor may change how the cell responds to a second neurotransmitter that acts through a ligand-activated channel. Signaling through metabotropic receptors can also have effects on the postsynaptic cell that don‘t involve ion channels at all. Eg., The muscarinic class acetylcholine receptors, most of the biogenic amine receptors, and all of the neuropeptide receptors are metabotropic receptors. 4. Enumerate the characteristics of neurites The processes of neurons are called neurites. These are of two types: dendrites or dendrons and an axon or axis cylinder or neuraxon.

 Most sensitive part of neuron is axon hillock.  The axon contains neurofibrils and neurotubules but does not have Nissl's granules, Golgi complex, ribosomes, pigment granules, fat globules, etc.  In the absence of Nissl's granules, the axon depends on the cell body for the supply of proteins.  The cell membrane of the axon is called axolemma and its cytoplasm is known as axoplasm.  The axon ends in a group of branches, the terminal arborizations (= axon terminals or telodendria).  When terminal arborizations of the axon meet the dendrites of another neuron to form a synapse they form synaptic knobs (= end plates).  The synaptic knobs contain mitochondria and secretory vesicles. On muscle fibres and gland cells, the terminal arborizations end as motor end plates.  Each axon may also possess lateral or branches called collateral fibres which are usually much finer than the main axonal process.  The axon conducts nerve impulses away from the cell body, therefore, called an efferent process.  A synapse is a site of junction between terminal arborizations of axon of one neuron and the dendrites of another neuron.  Each neuron receives an impulse through its dendrites and passes it on to the next neuron through synapse.  A fresh impulse is set up in the dendrites at the synapse with the help of chemicals called neurotransmitters, such as acetylcholine produced by the secretory vesicles of the synaptic knobs.  Acetylcholine is the first neurotransmitter to be discovered.

5. Explain the role of thyroid on brain development In vertebrate anatomy, the thyroid gland or simply, the thyroid, is one of the largest endocrine glands in the body. The thyroid gland is found in the neck, inferior to (below) the thyroid cartilage (also known as the Adam's Apple) and at approximately the same level as the cricoid cartilage. The thyroid controls how quickly the body uses energy, makes proteins, and controls how sensitive the body should be to other hormones. The thyroid gland participates in these processes by producing thyroid hormones, the principal ones being triiodothyronine (T3) and thyroxine (T4). These hormones regulate the rate

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES of metabolism and affect the growth and rate of function of many other systems in the body. T3 and T4 are synthesized utilizing both iodine and tyrosine. The thyroid gland also produces calcitonin, which plays a role in calcium homeostasis. The thyroid gland is controlled by thyroid-stimulating hormone (TSH) produced by the pituitary and thyrotropin-releasing hormone (TRH) produced by the hypothalamus. Physiology The primary function of the thyroid is production of the hormones triiodothyronine (T3), thyroxine (T4), and calcitonin. Up to 80% of the T4 is converted to T3 by peripheral organs such as the liver, kidney and spleen. T3 is several times more powerful than T4, which is largely a prohormone, perhaps four or even ten times more active. T3 and T4 production and action

The system of the thyroid hormonesT3 and T4. Thyroxine (T4) is synthesised by the follicular cells from free tyrosine and on the tyrosine residues of the protein called thyroglobulin (Tg). Iodine is captured with the "iodine trap" by the hydrogen peroxide generated by the enzyme thyroid peroxidase (TPO) and linked to the 3' and 5' sites of the benzene ring of the tyrosine residues on Tg, and on free tyrosine. Upon stimulation by the thyroid-stimulating hormone (TSH), the follicular cells reabsorb Tg and cleave the iodinated tyrosines from Tg in lysosomes, forming T4 and T3 (in T3, one iodine atom is absent compared to T4), and releasing them into the blood. Deiodinase enzymes convert T4 to T3. Thyroid hormone secreted from the gland is about 80-90% T4 and about 10-20% T3. Cells of the developing brain are a major target for the thyroid hormones T3 and T4. Thyroid hormones play a particularly crucial role in brain maturation during fetal development. A transport protein that seems to be important for T4 transport across the blood-brain barrier (OATP1C1) has been identified. A second transport protein (MCT8) is important for T3 transport across brain cell membranes. T3 can activate phosphatidylinositol 3-kinase by a mechanism that may be cytoplasmic in origin or may begin at integrin alpha V beta3. Pregnant women on a diet that is severely deficient of iodine can give birth to infants who can present with thyroid hormone deficiency (congenital hypothyroidism), manifesting in problems of physical growth and development as well as brain development (a condition referred to as endemic cretinism). In many developed countries, newborns are routinely tested for congenital hypothyroidism as part of newborn screening. Children with congenital

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES hypothyroidism are treated supplementally with levothyroxine, which facilitates normal growth and development. Thyroxine is critical to the regulation of metabolism and growth throughout the animal kingdom. Among amphibians, for example, administering a thyroid-blocking agent such as propylthiouracil (PTU) can prevent tadpoles from metamorphosing into frogs; in contrast, administering thyroxine will trigger metamorphosis.

6. Describe the influence of hormones on the development of neuronal function. (Nov.2016)

 In addition to the nervous system, the endocrine system is a major communication system of the body. While the nervous system uses neurotransmitters as its chemical signals, the endocrine system uses hormones. The pancreas, kidneys, heart, adrenal glands, gonads, thyroid, parathyroid, thymus, and even fat are all sources of hormones. The endocrine system works in large part by acting on neurons in the brain, which controls the pituitary gland. The pituitary gland secretes factors into the blood that act on the endocrine glands to either increase or decrease hormone production. This is referred to as a feedback loop, and it involves communication from the brain to the pituitary to an endocrine gland and back to the brain.  This system is very important for the activation and control of basic behavioral activities, such as sex; emotion; responses to stress; and eating, drinking, and the regulation of body functions, including growth, reproduction, energy use, and metabolism. The way the brain responds to hormones indicates that the brain is very malleable and capable of responding to environmental signals.  The brain contains receptors for thyroid hormones (those produced by the thyroid) and the six classes of steroid hormones, which are synthesized from cholesterol — androgens, estrogens, progestins, glucocorticoids, mineralocorticoids, and vitamin D. The receptors are found in selected populations of neurons in the brain and relevant organs in the body. Thyroid and steroid hormones bind to receptor proteins that in turn bind to DNA and regulate the action of genes. This can result in long-lasting changes in cellular structure and function.  The brain has receptors for many hormones; for example, the metabolic hormones insulin, insulin-like growth factor, ghrelin, and leptin. These hormones are taken up from the blood and act to affect neuronal activity and certain aspects of neuronal structure.  In response to stress and changes in our biological clocks, such as day and night cycles and jet lag, hormones enter the blood and travel to the brain and other organs. In the brain, hormones alter the production of gene products that participate in synaptic neurotransmission as well as affect the structure of brain cells. As a result, the circuitry of the brain and its capacity for neurotransmission are changed over a course of hours to days. In this way, the brain adjusts its performance and control of behavior in response to a changing environment.  Hormones are important agents of protection and adaptation, but stress and stress hormones, such as the glucocorticoid cortisol, can also alter brain function, including the brain‘s capacity to learn.  Reproduction in females is a good example of a regular, cyclic process driven by circulating hormones and involving a feedback loop: The neurons in the hypothalamus

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

produce gonadotropin-releasing hormone (GnRH), a peptide that acts on cells in the pituitary. In both males and females, this causes two hormones — the follicle-stimulating hormone (FSH) and the luteinizing hormone (LH) — to be released into the bloodstream. In females, these hormones act on the ovary to stimulate ovulation and promote release of the ovarian hormones estradiol and progesterone. In males, these hormones are carried to receptors on cells in the testes, where they promote spermatogenesis and release the male hormone testosterone, an androgen, into the bloodstream. Testosterone, estrogen, and progesterone are often referred to as sex hormones.  In turn, the increased levels of testosterone in males and estrogen in females act on the hypothalamus and pituitary to decrease the release of FSH and LH. The increased levels of sex hormones also induce changes in cell structure and chemistry, leading to an increased capacity to engage in sexual behavior. Sex hormones also exert widespread effects on many other functions of the brain, such as attention, motor control, pain, mood, and memory.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

UNIT – IV PART – A 1. Define receptor. Receptor may refer to:  Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse  Receptor , in biochemistry, a protein molecule that receives and responds to a neurotransmitter, or other substance  Immune receptor, a special case of biochemical receptor that occurs on the surface of immunocytes and binds to antigens 2. Write short note on sense of olfaction.  Olfaction is the sense of smell.  Mediated by specialized sensory cells of the nasal cavity of vertebrates, and, by analogy, sensory cells of the antennae of invertebrates.  Many vertebrates, including most mammals and reptiles, have two distinct olfactory systems—the main olfactory system, and the accessory olfactory system (mainly used to detect pheremones).  For air-breathing animals- the main olfactory system detects volatile chemicals, and the accessory olfactory system detects fluid-phase chemicals.  For water-dwelling organisms, e.g., fish or crustaceans, the chemicals are present in the surrounding aqueous medium.  Olfaction, along with taste, is a form of chemoreception.  The chemicals themselves which activate the olfactory system, generally at very low concentrations, are called odorants. 3. Give the functions of Olfactory lobes. (AU Nov. 2016)  The olfactory lobe (or olfactory bulb) is the structure within the brain that receives neural input from the nasal cavity, thus processing the sense of smell.  The cells within the nasal cavity detect odors in the form of chemical particulates within the air and send the received information to the olfactory bulb.  The olfactory bulb separate odors apart, amplify sensitivity to odors, identify important odors and send the information to higher level areas of the brain for further information processing.  discriminating among odors  enhancing sensitivity of odor detection  filtering out many background odors to enhance the transmission of a few select odors  Permitting higher brain areas involved in arousal and attention to modify the detection or the discrimination of odors. 4. What are pain receptors? (AU Nov. 2013)  Any one of the many free nerve endings throughout the body that warn of potentially harmful changes in the environment, such as excessive pressure or temperature.  The free nerve endings constituting most of the pain receptors are located chiefly in the epidermis and in the epithelial covering of certain mucous membranes.  They also appear in the stratified squamous epithelium of the cornea, in the root sheaths and the papillae of the hairs, and around the bodies of sudoriferous glands.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 The terminal ends of pain receptors consist of unmyelinated nerve fibers that often anastomose into small knobs between the epithelial cells.  Any kind of stimulus, if it is intense enough, can stimulate the pain receptors in the skin and the mucosa, but only radical changes in pressure and certain chemicals can stimulate the pain receptors in the viscera. 5. Write short notes on taste buds. (AU Nov. 2015)  Taste buds contain the receptors for taste.  They are located around the small structures on the upper surface of the tongue, soft palate, upper esophagus and epiglottis, which are called papillae.  These structures are involved in detecting the five (known) elements of taste perception: salty, sour, bitter, sweet, and savory, via small openings in the tongue epithelium, called taste pores  Parts of the food dissolved in saliva come into contact with taste receptors.  These are located on top of the taste receptor cells that constitute the taste buds.  The taste receptor cells send information detected by clusters of various receptors and ion channels to the gustatory areas of the brain via the seventh, ninth and tenth cranial nerves.  On average, the human tongue has 2,000–8,000 taste buds. 6. List various sensory receptors distributed in human body. (AU Nov. 2017)  Chemoreceptors detect the presence of chemicals.  Thermoreceptors detect changes in temperature.  Mechanoreceptors detect mechanical forces.  Photoreceptors detect light during vision.  More specific examples of sensory receptors are baroreceptors, propioceptors, hygroreceptors, and osmoreceptors.  Sensory receptors perform countless functions in our bodies mediating vision, hearing, taste, touch, and more. 7. Explain the image formation in eye.  Light from our surroundings enters our eye through the dioptric media --- cornea, lens, aqueous humour and vitreous body.  Among these, the anterior part of the cornea accounts for providing nearly 2/3 of the refractive power, because it has a highly curved surface and high refractive index.  Light stimulates the photoreceptors on our retina to produce nerve impulses, which will travel along the optic nerve to the of our brain.  The image formed on the retina is real, inverted and smaller. However, on interpretation by the brain, the images will be upright. 8. Define tactile sensation.  The Tactile or somatosensory system is a diverse sensory system comprising the receptors and processing centres to produce the sensory modalities such as touch, temperature, proprioception (body position), and nociception (pain).  The sensory receptors cover the skin and epithelia, skeletal muscles, bones and joints, internal organs, and the cardiovascular system.  While touch is considered one of the five traditional senses, the impression of touch is formed from several modalities. Or

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 Tactile sensation refers to the sense of touch, specifically the information received from varying pressure or vibration against the skin.  Tactile sensation is considered a somatic sensation, meaning it originates at the surface of the body, rather than internally.  Nerve endings designed to act as tactile receptors are located in the dermis of the skin and send signals to the brain, which the brain then interprets as sensations.  Some areas of the body are more sensitive than others because they have more nerve endings. For example, a fingertip, one of the most sensitive parts of the body, has about 100 nerve endings. 9. What is Cochlea? (AU Nov. 2015)  The cochlea is a portion of the inner ear that looks like a snail shell  The cochlea is filled with a watery liquid, which moves in response to the vibrations coming from the middle ear via the oval window.  As the fluid moves, thousands of "hair cells" are set in motion, and convert that motion to electrical signals that are communicated via neurotransmitters to many thousands of nerve cells.  These primary auditory neurons transform the signals into electrical impulses known as action potential, which travel along the auditory nerve to structures in the brainstem for further processing. 10. What is trigeminal neuralgia? (AU Nov. 2016)  Trigeminal neuralgia (TN), also called tic douloureux, is a chronic pain condition that affects the trigeminal or 5th cranial nerve  TN is a form of neuropathic pain (pain associated with nerve injury or nerve lesion.)  The typical or "classic" form of the disorder (called "Type 1" or TN1) causes extreme, sporadic, sudden burning or shock-like facial pain that lasts anywhere from a few seconds to as long as two minutes per episode.  The ―atypical‖ form of the disorder (called "Type 2" or TN2), is characterized by constant aching, burning, stabbing pain of somewhat lower intensity than Type 1. 11. Write short notes on Retina.  The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye.  The optics of the eye creates an image of the visual world on the retina, which serves much the same function as the film in a camera.  Light striking the retina initiates a cascade of chemical and electrical events that ultimately trigger nerve impulses.  These are sent to various visual centers of the brain through the fibers of the optic nerve. 12. Define skeletal muscle.  Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system.  It is one of three major muscle types, the others being cardiac and smooth muscle.  Most skeletal muscle is attached to bones by bundles of collagen fibers known as tendons. Skeletal muscle is made up of individual components known as muscle fibers. These fibers are formed from the fusion of developmental myoblasts (a type of embryonic progenitor cell that gives rise to a muscle cell).

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 The myofibers (muscle fiber) are long, cylindrical, multinucleated cells composed of actin and myosin myofibrils repeated as a sarcomere, the basic functional unit of the cell and responsible for skeletal muscle's striated appearance and forming the basic machinery necessary for muscle contraction.  The term muscle refers to multiple bundles of muscle fibers held together by connective tissue. 13. What is the role of Ca2+ ions in the contraction of skeletal muscles? (AU Nov. 2017)  The release of Ca2+, after receiving the nerve impulse, liberates the myosin's binding site on actin filaments. This enables a contraction,  A return of the calcium in the sarcoplasmic reticulum allows the muscle to relax. 14. Describe muscle contraction.

 Action potential in a motor neuron triggers the release of Ca2+ ions from the sarcoplasmic reticulum  Calcium ions bind to troponin (on actin) and cause tropomyosin to move, exposing binding sites for the myosin heads  The actin filaments and myosin heads form a cross-bridge that is broken by ATP  ATP hydrolysis causes the myosin heads to swivel and change orientation  Swiveled myosin heads bind to the actin filament before returning to their original conformation (releasing ADP + Pi)  The repositioning of the myosin heads move the actin filaments towards the centre of the sarcomere  The sliding of actin along myosin therefore shortens the sarcomere, causing muscle contraction 15. Describe ear.  Human ear, organ of hearing and equilibrium that detects and analyzes sound by transduction (or the conversion of sound waves into electrochemical impulses)  It maintains the sense of balance (equilibrium). 16. What is tympanic membrane? (AU Nov. 2014)  Tympanic membrane (eardrum) is a thin layer of tissue in the human ear that receives sound vibrations from the outer air and transmits them to the auditory ossicles, which are tiny bones in the tympanic (middle-ear) cavity.  It also serves as the lateral wall of the tympanic cavity, separating it from the external auditory canal.  The membrane lies across the end of the external canal and looks like a flattened cone with its tip (apex) pointed inward.  The edges are attached to a ring of bone, the tympanic annulus. PART– B 1. Explain the olfactory sensation Smell is our distant chemical sense. We can discern information about the chemical composition of substances before coming into more direct contact with them.  For many animals, smell is the most important sense.  Smell is an important part of taste. Many qualities of foods that we think we taste are actually a function of smell.

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

Anatomy of Smell

 The Olfactory Mucosa is a dime-sized region located high inside the nasal cavity and is the site of olfactory transduction.  The olfactory mucosa contains olfactory receptor neurons.

 Olfactory receptor neurons have cilia (little hair-like projections) which contain the olfactory receptor proteins.

The Smell Pathway

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 Olfactory transduction occurs when odorant molecules reach the olfactory mucosa and bind to the olfactory receptor proteins on the cilia of the olfactory receptor neurons.  When odorants bind to the receptor site, the receptor protein changes shape which in turn triggers the flow of ions across the receptor-cell membrane and an electrical response is triggered in the cilium.  Electrical responses in the cilia spread to the rest of the receptor cell, and from there are passed onto the olfactory bulb of the brain in the olfactory nerve.  There are about 1,000 different types of receptor proteins each sensitive to different odorants.  We have a total of about 10 million receptor neurons. Each receptor neuron has about 1,000 similar receptor proteins. Because there are 1,000 different receptor proteins, there are also 1,000 different receptor neurons.  Inputs from similar receptor neurons go to similar glomeruli (collections of cells within the olfactory bulb). Because there are 1,000 different types of receptor neurons, there are 1,000 different types of glomeruli.  From the olfactory bulb, mitral cells and tufted cells carry olfactory information to the olfactory cortex, and to the orbitofrontal cortex.

2. Explain the sense of taste  Taste is a gate-keeper sensory mechanism designed to test food and other substances before they enter the body.  Things that are potentially useful for the body tend to taste good, and things that are potentially harmful taste bad. Anatomy of Taste

1. The tongue contains many ridges and valleys called papillae. There are four types of papillae: . Filiform papillae: cone shaped & found all over the tongue (which is why tongues look rough) . Fungiform papillae: mushroom shaped & found at the tip and sides of the tongue . Foliate papillae: a series of folds along the sides of the tongue . Circumvallate papillae: shaped like flat mounds surrounded by a trench & found at the back of the tongue 2. All papillae except filiform contain taste buds (so the very center of your tongue which only has filiform papillae is "taste-blind")

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

3. Each taste bud contains a number of taste cells which have tips that protrude into the taste pore.

The Taste Pathway 4. Transduction occurs when different taste substances cause a change in the flow of ions across the membrane of a taste cell. 5. Different substances affect the membrane in different ways. . Bitter and sweet substances bind into receptor sites which release other substances into the cell. . Sour substances contain H+ ions that block channels in the membrane. . Salty substances break up into Na+ ions which flow through the membrane directly into the cell.

6. Electrical signals generated in the taste cells are transmitted in three pathways: . The chorda tympani nerve conducts signals from the front and sides of the tongue. . The glosso-pharyngeal nerve conducts signals from the back of the tongue. . The vagus nerve conducts taste signals from the mouth and the larynx. 7. These three nerves make connections in the brain stem in the nucleus of the solitary tract (NST) before going on to the thalamus and then to two regions of the frontal lobe (the insula and the frontal operculum cortex). 2. Explain the physiology of vision. Physiology of vision 1. Refraction of light entering the eye 2. Focusing of image on the retina by accommodation of lens 3. Convergence of image 4. Photo-chemical activity in retina and conversion into neural impulse 5. Processing in brain and perception Refraction:

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

. Light wave travels parallel to each other but they bend when passes from one medium to another. This phenomenon is called refraction. . Before light reach retina it passes through cornea, aqueous humor, lens vitrous humor, so refraction takes place in every medium before it falls on retina. . In normal eye, light wave focused on retina. . However in myopic eye (short sightedness) light focused in front of retina. So this defect can be treated by using cancave lens. . In case of far sightedness light focused behind retina, so no image is formed. This defect can be treated by using convex lens. Accommodation: . Accommodation is a reflex process to bring light rays from object into perfect focus on retina by adjusting the lens. . When an object lying less than 6 meter away is viewed, image formed behind retina. But due to accommodation of lens image formed in retina and we can see the object. . For accommodation to view closer object, ciliary muscle contract and lens become thick which causes focus on closer object. . Similarly, when distant object is viewed, ciliary muscles relaxes, so the tension of ligament become greater which pull lens and lens become thinner, due to which image forms on retina. . The normal eye is able to accommodate light from object about 25 cm to infinity.

Convergence: . Human eye have binocular vision, it means although we have two eye, we perceive single image . In binocular vision, two eye ball turns slightly inward to focus a close object so that both image falls on corresponding points on retina at same time. This phenomenon is called convergence. Photo-chemical activity in retina and conversion into neural impulse 1. Photochemical activity in rods: . Each eye contains 125 million rods which are located in neuro-retina. . Rods contains light sensitive pigment-rhodopsin.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

. Rhodopsin is a molecule formed by combination of a protein scotopsin and a light sensitive small molecule retinal (retinene). . Retinene (retinal) is a carotenoid molecule and is derivative of vitamin A (retinol). . Retinal exists in two isomeric form- cis and trans according to light condition. . The extra cellular fluids surrounding rod cells contains high concentration of Na+ ion and low concentration of K+ ions while concentration of Na+ is low and K+ is high inside rod cells. The concentration is maintained by Na-K pump. . In resting phase, K+ tends to move outside the rod cells creating slightly –ve charge inside. . When light is falls on rod cell, it is absorbed by rhodopsin and it breaks into scotopsin and 11 cis- retinal. The process is known as bleaching. . 11 cis-retinal absorb photon of light and change into all trans-retinal which inturn activates scotopsin into enzyme. . This reaction produces large amount of transducin which activates another enzyme phosphodiesterase. . Phosphodiesterase hydrolyses cGMP which causes to cease the flow of Na+ ion inside rod cell. This causes increased negative charge inside cell creating hyperpolarized state. . Hyperpolarized rod cells transmit the neural signal to bipolar cell. . Bipolar cell, amacrine cell and ganglion cell process the neural signal and generate action potential to transmit to brain via optic nerve.

. 2. Photochemical activity in cones: . Each eye contains 7 million cone cells. . The neural activity in cone cell is similar to that of rod cell but there are three different types of cone cells and each cone cell contains different photo-pigment and are sensitive to red, green and blue. . Like rod, cone cell contains iodopsin as photo-pigment which is composed of 11 cis-retinal and photopsin. . The perception of color depends upon which cones are stimulated. . The final perceived color is combination of all three types of cone cell stimulated depending upon the level of stimulation.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

. The proper mix of all three colors produce the perception of white and absence of all color produce perception of black. Processing of image in brain and perception:

. All visual information originates in retina due to stimulation of rods and cones are conveyed to brain. . Retina contains 5 types of cells and they are interconnected by synapse. These cells are photoreceptor cells (rod and cone), bipolar cell, ganglion cell, horizontal cell and amacrine cell. . Photoreceptor cells, bipolar cells and ganglion cells transmit impulse directly from retina to brain. . The nerve fiber of ganglion cells from both eyes carries impulse along two optic nerve. . The optic nerves meets at optic chiasma where fibers from nasal half of each retina cross- over but fibers from temporal half of each retina do not cross-over. . The optic nerve after crossing the chiasma is called as optic tract. . Each optic tract continues posteriorly until it synapse with neuron in thalamus called lateral geniculate body which project to primary visual cortex in occipital lobe of cerebrum and image is perceived. 3. Explain the physiology of hearing The process of hearing has evolved over time to provide critical sensory information that is essential to our everyday lives. Like other sensory organs, the ear is responsible for gathering data from the environment and translating it into a form that our brains can understand. In hearing, this process begins with sound waves.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

Sound waves are in essence vibrations carried through the air. The process in which our brains interpret those vibrations to sound can be divided into three measures: collecting the vibrations, converting those vibrations into mechanical energy, and relaying each as an electrical impulse to be interpreted as sound by the brain. Similarly, the ear itself can be divided into three distinct anatomical areas that are responsible for these distinct processes:  Outer Ear Sound waves are funneled into the ear via the auricle and through the external auditory canal to the tympanic membrane (eardrum) where the vibrations are then converted into mechanical energy.  Middle Ear The tympanic membrane is attached to the first in a chain of three small bones (malleus, incus, and stapes) known as the ossicular chain. The three bones propel one another sequentially, ultimately striking the oval window.  Inner Ear The primary component of the inner ear in the process of interpreting sound is the cochlea, a coiled chamber of fluid. The cochlea‘s oval window is the membranous barrier between the middle and inner ear. When the last bone in the middle ear strikes the oval window, the resonance is carried through fluid called perilymph. The bottom layer of the cochlea is carpeted by a layer of microscopic hair cells, each stimulated by specific frequencies, or pitches, of sound waves/vibrations. Once stimulated by the movement of the perilymph fluid, they relay that information to the brain via the auditory nerve to be interpreted in the brain as sound. 4. Write the Mechanism of touch and pain

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 The sense of touch is located in the skin, which is composed of three layers: the epidermis, dermis, and hypodermis.  Different types of sensory receptors, varying in size, shape, number, and distribution within the skin, are responsible for relaying information about pressure, temperature, and pain.  The largest touch sensor, the Pacinian corpuscle, is located in the hypodermis, the innermost thick fatty layer of skin, which responds to vibration.  Free nerve endings—neurons that originate in the spinal cord, enter and remain in the skin—transmit information about temperature and pain from their location at the bottom of the epidermis.  Hair receptors in the dermis, which are wrapped around each follicle, respond to the pressure produced when the hairs are bent.  All the sensory receptors respond not to continued pressure but rather to changes in pressure, adapting quickly to each new change, so that, for example, the skin is unaware of the continual pressure produced by clothes.  Once stimulated by sensation, the receptors trigger nerve impulses which travel to the somatosensory cortex in the parietal lobe of the brain, where they are transformed into sensations.  Sensitivity to touch varies greatly among different parts of the body. Areas that are highly sensitive, such as the fingers and lips, correspond to a proportionately large area of the sensory cortex. PAIN Pain is a vital function of the human body, involving nociceptors and the central nervous system (CNS) to transmit messages from noxious stimuli to the brain. The mechanism for neuropathic pain is distinct as it is caused by injury to the nervous system itself and can occur without the presence of noxious stimuli. Nociceptors Nociceptors are sensory receptors that are responsible for detecting harmful or noxious stimuli and transmitting electrical signals to the nervous system. The receptors are present in skin,

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES viscera, muscles, joints and meninges to detect a range of stimuli, which may be mechanical, thermal or chemical in nature. There are two main types of nociceptors: I. C-fibres are the most common type and are slow to conduct and respond to stimuli. As the proteins in the membrane of the receptor convert the stimuli into electrical impulses that can be carried throughout the nervous system. II. A-delta fibers are known to conduct more rapidly and convey messages of sharp, momentary pain.  Additionally, there are silent nociceptors that are usually unresponsive to stimuli but can be ―awoken‖ with high-intensity mechanical stimuli in response to chemical mediators in the body.  Nociceptors have a variety of voltage-gated channels for transduction that lead to a set of action potentials to initiate the electrical signaling into the nervous system.  The excitability and behavior of the cell depend on the types of channels present in the nociceptor.  It is important to distinguish between nociception and pain when considering the mechanism of pain.  Nociception is the normal response of the body to noxious stimuli, including reflexes below the suprathreshold that protect the body from harm. Pain is only perceived when superthreshold for the nociceptors to reach an action potential and initiate the pain pathway is reached, which is relatively high. Central Nervous System  The nociceptors conduct the electrical signaling message to the dorsal horn of the spinal cord, where a complex array of neurons are involved in the synaptic connections that process nociception and pain.  The generation of pain in the central nervous system is due to a combination of pathways that are involved in the propagation of signals to the cerebral cortex.  The perception of pain results from processing of the electrical signals in various regions of the brain. This explains the varied responses and emotional reactions when an individual experiences pain. Neuropathic Pain Mechanism  The mechanisms that lead to the development of persistent neuropathic pain are more complex than nociceptive pain and should be thought of as distinct.  Neuropathic pain occurs primarily as a result of injury to the nerves involved in the pain pathways in the nervous system, leading to an alteration in the way pain is processed.  This usually causes increased pain signal transmission, to the extent that innocuous stimuli may cause a sensation of pain.  Hyperalgesia is a type persistent inflammatory pain that involves increased excitability and nervous response to noxious stimuli, leading to higher sensitivity to pain.  There are also some psychological factors that can influence the experience and extent of pain, known of modulatory influences. These include stress, fear and anxiety and it is widely believed that high levels of these factors can initiate, worsen or prolong episodes of pain in susceptible individuals. 5. Write short note on skeletal muscle

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system. It is one of three major muscle types, the others being cardiac and smooth muscle. As its name suggests, most skeletal muscle is attached to bones by bundles of collagen fibers known as tendons.  Skeletal muscle is made up of individual components known as muscle fibers.  These fibers are formed from the fusion of developmental myoblasts (a type of embryonic progenitor cell that gives rise to a muscle cell).  The myofibers (muscle fiber) are long, cylindrical, multinucleated cells composed of actin and myosinmyofibrils repeated as a sarcomere, the basic functional unit of the cell and responsible for skeletal muscle's striated appearance and forming the basic machinery necessary for muscle contraction.  The term muscle refers to multiple bundles of muscle fibers held together by connective tissue. Muscle fibers  Individual muscle fibers are formed during development from the fusion of several undifferentiated immature cells known as myoblasts into long, cylindrical, multi-nucleated cells.  Differentiation into this state is primarily completed before birth with the cells continuing to grow in size thereafter.  Skeletal muscle exhibits a distinctive banding pattern when viewed under the microscope due to the arrangement of cytoskeletal elements in the cytoplasm of the muscle fibers.  The principal cytoplasmic proteins are myosin and actin (also known as "thick" and "thin" filaments, respectively) which are arranged in a repeating unit called a sarcomere.  The interaction of myosin and actin is responsible for muscle contraction.  There are two principal ways to categorize muscle fibers: the type of myosin (fast or slow) present, and the degree of oxidative phosphorylation that the fiber undergoes.  Skeletal muscle can thus be broken down into two broad categories: Type I and Type II. Type I fibers appear red due to the presence of the oxygen binding protein myoglobin.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 These fibers are suited for endurance and are slow to fatigue because they use oxidative metabolism to generate ATP.  Type II fibers are white due to the absence of myoglobin and a reliance on glycolytic enzymes.  These fibers are efficient for short bursts of speed and power and use both oxidative metabolism and anaerobic metabolism depending on the particular sub-type. These fibers are quicker to fatigue 6. Describe the process of muscle contraction For a contraction to occur there must first be a stimulation of the muscle in the form of an impulse (action potential) from a motor neuron (nerve that connects to muscle).

 One motor neuron does not stimulate the entire muscle but only a number of muscle fibres within a muscle.  The individual motor neuron plus the muscle fibres it stimulates, is called a motor unit. The motor end plate (also known as the neuromuscular junction) is the junction of the motor neurons axon and the muscle fibres it stimulates.  When an impulse reaches the muscle fibres of a motor unit, it stimulates a reaction in each sarcomere between the actin and myosin filaments. This reaction results in the start of a contraction and the sliding filament theory.  The reaction, created from the arrival of an impulse stimulates the 'heads' on the myosin filament to reach forward, attach to the actin filament and pull actin towards the centre of the sarcomere. This process occurs simultaneously in all sarcomeres, the end process of which is the shortening of all sarcomeres.  Troponin is a complex of three proteins that are integral to muscle contraction. Troponin is attached to the protein tropomyosin within the actin filaments, as seen in the image below. When the muscle is relaxed tropomyosin blocks the attachment sites for the myosin cross bridges (heads), thus preventing contraction.  When the muscle is stimulated to contract by the nerve impulse, calcium channels open in the sarcoplasmic reticulum (which is effectively a storage house for calcium within the muscle) and release calcium into the sarcoplasm (fluid within the muscle cell). Some of this calcium attaches to troponin which causes a change in the muscle cell that moves tropomyosin out of the way so the cross bridges can attach and produce muscle contraction.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

In summary the sliding filament theory of muscle contraction can be broken down into four distinct stages, these are; 1. Muscle activation: The motor nerve stimulates an action potential (impulse) to pass down a neuron to the neuromuscular junction. This stimulates the sarcoplasmic reticulum to release calcium into the muscle cell. 2. Muscle contraction: Calcium floods into the muscle cell binding with troponin allowing actin and myosin to bind. The actin and myosin cross bridges bind and contract using ATP as energy (ATP is an energy compound that all cells use to fuel their activity. 3. Recharging: ATP is re-synthesised (re-manufactured) allowing actin and myosin to maintain their strong binding state 4. Relaxation: Relaxation occurs when stimulation of the nerve stops. Calcium is then pumped back into the sarcoplasmic reticulum breaking the link between actin and myosin. Actin and myosin return to their unbound state causing the muscle to relax. Alternatively relaxation

(failure) will also occur when ATP is no longer available. In order for a skeletal muscle contraction to occur; 1. There must be a neural stimulus 2. There must be calcium in the muscle cells 3. ATP must be available for energy Regulation  A nerve impulse causes the release of acetylcholine to the synaptic cleft, which binds to receptors on the motor end plate, triggering a series of electrical events on the sarcolemma.

 An action potential, or wave of depolarization of significant strength, opens voltage regulated Ca2+ channels in the axon terminal.  Ca2+ influx into the axon stimulates fusion of synaptic vesicles with the axon terminal plasma membrane and the release of neurotransmitter (Ach) in the synaptic cleft.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 Ach diffuses across the synaptic cleft, binds to receptors on the motor endplate, and opens chemically-regulated ion channels in the sarcolemma.  Ach is broken down by acetylcholine esterase, which terminates stimulation of the sarcolemma  When acetylcholine binding with receptors opens chemically-regulated ion channels in the sarcolemma Na+ ions enter the cell faster than K+ ions exit, which makes the membrane potential slightly less negative (depolarizes the membrane).  Positively charged ions move across the inside of the sarcolemma into more negative areas - this is a wave of depolarization. The depolarization can be measured (just like a resting membrane potential) and is referred to as a graded local potential, or in this specific case, an endplate potential.  Generation of an action potential across the sarcolemma occurs in response to the wave of depolarization reaching a voltage regulated Na+ channel with sufficient strength to open it.  The degree of depolarization required to open a voltage regulated Na+ channel is called threshold (typically 15 - 20 mV above the resting membrane potential).  The influx of Na+ through voltage regulated channels opens voltage regulated K+ channels.  As K+ leaves the cell it becomes repolarized and can be stimulated again.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

UNIT – V PART – A 1. Define memory. What are the three kinds of memory? (AU Nov 2017)  Memory is the faculty of the mind by which information is encoded, stored, and retrieved.  Memory is vital to experiences and related to limbic systems, it is the retention of information over time for the purpose of influencing future action.  If we could not remember past events, we could not learn or develop language, relationships, nor personal identity.  Types of memory:   Short-term memory or  Long term memory 2. Define short term memory  Short-term memory (primary or active memory) is the capacity for holding a small amount of information in mind in an active, readily available state for a short period of time.  For example, short-term memory can be used to remember a phone number that has just been recited.  The duration of short-term memory (when rehearsal or active maintenance is prevented) is believed to be in the order of seconds.  Short-term memory is supported by transient patterns of neuronal communication, dependent on regions of the frontal lobe (especially dorsolateral prefrontal cortex) and the parietal lobe. 3. Write short notes on long term memory  Long-term memory (LTM) is the stage of the Atkinson–Shiffrin memory model where informative knowledge is held indefinitely.  It is defined in contrast to short-term and working memory that persists for only about 18 to 30 seconds.  Long-term memory is commonly labelled as (declarative), as well as , , , and ().  Long-term are maintained by more stable and permanent changes in neural connections widely spread throughout the brain.  The hippocampus is essential (for learning new information) to the consolidation of information from short-term to long-term memory, although it does not seem to store information itself.  Without the hippocampus, new memories are unable to be stored into long-term memory, and there will be a very short attention span.  Furthermore, it may be involved in changing neural connections for a period of three months or more after the initial learning.  One of the primary functions of sleep is thought to be improving consolidation of information, as several studies have demonstrated that memory depends on getting sufficient sleep between training and test.

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 Additionally, data obtained from neuroimaging studies have shown activation patterns in the sleeping brain which mirror those recorded during the learning of tasks from the previous day, suggesting that new memories may be solidified through such rehearsal 4. List out memory disorders.  Memory disorders can range from mild to severe  They all result from some kind of neurological damage to the structures of the brain, thus hindering the storage, retention and recollection of memories.  Memory disorders can be progressive, like Alzheimer's or Huntington‘s disease,  Or immediate, like those resulting from traumatic head injury.  Most disorders are exacerbated by the effects of ageing, which remains the single greatest risk factor for neurodegenerative diseases in general.  Loss of memory is known as . There are many sorts of amnesia, and by studying their different forms, it has become possible to observe apparent defects in individual sub- systems of the brain's memory systems, and thus hypothesize their function in the normally working brain.  Other neurological disorders such as Alzheimer's disease can also affect memory and cognition.  , or hyperthymesic syndrome, is a disorder which affects an individual's autobiographical memory, essentially meaning that they cannot forget small details that otherwise would not be stored.  Korsakoff's syndrome, also known as Korsakoff's psychosis, amnesic-confabulatory syndrome, is an organic brain disease that adversely affects memory.  While not a disorder, a common temporary failure of word retrieval from memory is the tongue phenomenon. Sufferers of Nominal (also called Anomia), however, do experience the tip-of-the-tongue phenomenon on an ongoing basis due to damage to the frontal and parietal lobes of the brain. 5 .Write short notes on REM sleep  Rapid eye movement sleep (REM sleep) is a normal stage of sleep characterized by the rapid movement of the eyes.  REM sleep is classified into two categories: tonic and phasic.  It was identified and defined by Nathaniel Kleitman and Eugene Aserinsky in the early 1950s.  Criteria for REM sleep includes not only rapid eye movement, but also low muscle tone and a rapid, low-voltage EEG; these features are easily discernible in a polysomnogram, the sleep study typically done for patients with suspected sleep disorders.  REM sleep in adult humans typically occupies 20–25% of total sleep, about 90–120 minutes of a night's sleep.  During a normal night of sleep, humans usually experience about four or five periods of REM sleep; they are quite short at the beginning of the night and longer toward the end  During REM, the activity of the brain's neurons is quite similar to that during waking hours; for this reason, the REM-sleep stage may be called paradoxical sleep. This means there are no dominating brain waves during REM sleep. 6. Explain the mechanism of motivation in behaviour  Motivation is the driving force which causes us to achieve goals.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 Motivation is said to be intrinsic or extrinsic.  The term is generally used for humans but, theoretically, it can also be used to describe the causes for animal behavior as well.  According to various theories, motivation may be rooted in a basic need to minimize physical pain and maximize pleasure, or it may include specific needs such as eating and resting, or a desired object, goal, state of being, ideal, or it may be attributed to less-apparent reasons such as altruism, selfishness, morality, or avoiding mortality.  Conceptually, motivation should not be confused with either volition or optimism.  Motivation is related to, but distinct from, emotion. 7. List out different types of feeding in animals There are many modes of feeding that animals exhibit, including:  Filter Feeding - obtaining nutrients from particles suspended in water  Deposit Feeding - obtaining nutrients from particles suspended in soil  Fluid Feeding - obtaining nutrients by consuming other organisms' fluids  Bulk Feeding - obtaining nutrients by eating all of an organism  Ram feeding and Suction feeding - ingesting prey via the fluids around

8. Describe the neural mechanism of hearing  The inner ear includes both the organ of hearing (the cochlea) and a sense organ that is attuned to the effects of both gravity and motion (labyrinth or vestibular apparatus).  The balance portion of the inner ear consists of three semi-circular canals and the vestibule.  The inner ear is encased in the hardest bone of the body. Within this ivory hard bone, there are fluid-filled hollows. Within the cochlea are three fluid filled spaces: the scala tympani, the scalavestibuli and the scala media. The eighth cranial nerve comes from the brain stem to enter the inner ear.  When sound strikes the ear drum, the movement is transferred to the footplate of the stapes, which presses it into one of its fluid-filled ducts through the oval window of cochlea.  The fluid inside this duct is moved, flowing against the receptor cells of the Organ of Corti, which fire.  These stimulate the spiral ganglion, which sends information through the auditory portion of the eighth cranial nerve to the brain. 9. Write short notes on encephalitis  Encephalitis is an acute inflammation of the brain.  It is usually caused by a foreign substance or a viral infection.  Symptoms for this disease include: headache, neck pain, drowsiness, nausea, and fever.  If caused by the West Nile virus, it may be lethal to humans, as well as birds and horses.  Encephalitis with meningitis is known as meningoencephalitis.  Symptoms include headache, fever, confusion, drowsiness, and fatigue. More advanced and serious symptoms include seizures or convulsions, tremors, , and memory problems. 10. What is Viral encephalitis?  Viral encephalitis can be either due to the direct effects of an acute infection, or as one of the sequelae of a latent infection.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 A common cause of encephalitis in humans is herpes simplex virus type I (HSE) which may cause inflammation of the brain. This can result in death.  Others include infection by Flaviviruses such as St. Louis encephalitis or West Nile virus, or Togaviruses such as Eastern equine encephalitis (EEE), Western equine encephalitis (WEE) and Venezuelen equine encephalitis (VEE). 11. What is Bacterial encephalitis?  It can be caused by a bacterial infection, such as bacterial meningitis, spreading directly to the brain (primary encephalitis), or may be a complication of a current infectious disease syphilis (secondary encephalitis).  Certain parasitic or protozoal infestations, such as toxoplasmosis, malaria, or primary amoebic meningoencephalitis, can also cause encephalitis in people with compromised immune. Lyme disease and/or Bartonellahenselae may also cause encephalitis. 12. Write short notes on Huntington’s diseases.  Huntington's disease is a rare neurological disorder that is inherited.  Degeneration of neuronal cells in the frontal lobe of the brain occurs. There is a progressive decline which results in abnormal movements.  It is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia.  It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea and is much more common in people of Western European descent than in those from Asia or Africa.  The disease is caused by an autosomal dominant mutation on either of an individual's two copies of a gene called Huntingtin, which means any child of an affected parent has a 50% risk of inheriting the disease.

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

13. Define Alzheimer's disease.  Alzheimer‘s is a neurodegenerative disease typically found in people over the age of 65 years.  Worldwide, approximately 24 million people have dementia; 60% of these cases are due to Alzheimer‘s.  The clinical sign of Alzheimer‘s is progressive cognition deterioration.  Alzheimer's disease (AD), also called senile dementia of the Alzheimer type, primary degenerative dementia of the Alzheimer's type, or simply Alzheimer's, is the most common form of dementia. This incurable, degenerative, and terminal disease was first described by German psychiatrist and neuropathologist Alois Alzheimer in 1906 and was named after him. 14. Define Parkinson's disease  Parkinson's disease is a degenerative disorder of the central nervous system that impairs motor skills, cognitive processes, and other functions. Parkinson‘s affects the motor skills and speech.  Symptoms may include bradykinesia (slow physical movement), muscle rigidity, and tremors.  Behavior, thinking, and sensation disorders are non-motor symptoms. The most obvious symptoms are motor-related, including tremor, rigidity, slowness of movement, and postural instability. Among non-motor symptoms are autonomic dysfunction and sensory and sleep difficulties.  Cognitive and behavioral problems, including dementia, are common in the advanced stages of the disease.  PD usually appears around the age of 60, although there are young-onset cases. 14. Write short notes on types of Autoimmune nervous system diseases.  Guillain-Barre syndrome is a neurological disorder in which the body's immune system attacks part of the peripheral nervous system. Symptoms vary from person to person and may be mild or severe. The first prominent symptom is weakness, and most often the weakness is felt in both legs. The weakness is accompanied by decreased feeling (paresthesia).  Lambert-Eaton myasthenic syndrome (LEMS) is an uncommon neuromuscular disorder characterized by weakness in muscles of the upper arms and upper legs, and less commonly, muscles of the neck, speech, swallowing, breathing and eye movement. It is caused by a disruption of electrical impulses between these nerve and muscle cells.  Multiple sclerosis (MS) is a demyelinating disease, a non-contagious chronic autoimmune disorder of the central nervous system which can present with a variety of neurological symptoms occurring in attacks or slowly progressing over time. Multiple sclerosis (MS) can be thought of as an inflammatory process involving different areas of the central nervous system (CNS) at various points in time.  Myasthenia gravis is an autoimmune disease that affects the transmission of signals from nerves to muscles. Myasthenia gravis is caused by a defect in the transmission of nerve impulses to muscles. It occurs when normal communication between the nerve and muscle is interrupted at the neuromuscular junction - the place where nerve cells connect with the muscles they control.  Transverse myelitis (TM) is an uncommon neurological syndrome caused by inflammation (a protective response which includes swelling, pain, heat, and redness) of the spinal cord, characterized by weakness, back pain, and bowel and bladder problems. It affects

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES one to five persons per million. Acute transverse myelitis is a neurological disorder caused by inflammation of the spinal cord, which damages or destroys myelin, the fatty insulating substance that covers nerve cells fibers.  Progressive multifocal leuko encephalopathy is an advancing viral inflammation of the white matter of the brain. Immuno suppressed people are more susceptible to this disorder than the general population. Evidence of the disease may be a person´s recent loss of coordination and weakness, progressing to a loss of language, visual problems and headaches. 15. How is sleep controlled? (AU Nov.2017)  Sleep is regulated by two parallel mechanisms -homeostatic regulation and circadian regulation  These are controlled by the hypothalamus and the suprachiasmatic nucleus (SCN), respectively.

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

PART – B 1. Describe the control mechanism of memory with illustrations. (AU Nov 2017) In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory. The late nineteenth and early twentieth century put memory within the paradigms of cognitive psychology. In recent decades, it has become one of the principal pillars of a branch of science called cognitive neuroscience, an interdisciplinary link between cognitive psychology and neuroscience. From an information processing perspective there are three main stages in the formation and retrieval of memory:  Encoding or registration (receiving, processing and combining of received information)  Storage (creation of a permanent record of the encoded information)  Retrieval, recall or recollection (calling back the stored information in response to some cue for use in a process or activity)  Often memory is understood as an informational processing system with explicit and implicit functioning that is made up of a sensory processor, short-term (or working) memory, and long-term memory.  This can be related to the neuron. The sensory processor allows information from the outside world to be sensed in the form of chemical and physical stimuli and attended to with various levels of focus and intent.  Working memory serves as an encoding and retrieval processor.  Information in the form of stimuli is encoded in accordance with explicit or implicit functions by the working memory processor.  The working memory also retrieves information from previously stored material. Finally, the function of long-term memory is to store data through various categorical models or systems Sensory memory: Sensory memory corresponds approximately to the initial 200–500 milliseconds after an item is perceived. The ability to look at an item, and remember what it looked like with just a second of observation, or memorisation, is an example of sensory memory. Short-term: Short-term memory allows recall for a period of several seconds to a minute without rehearsal. Its capacity is also very limited Long-term memory: The storage in sensory memory and short-term memory generally have a strictly limited capacity and duration, which means that information is available only for a certain period of time, but is not retained indefinitely. By contrast, long-term memory can store much larger quantities of information for potentially unlimited duration (sometimes a whole life span). Its capacity is immeasurably large. Physiology Brain areas involved in the such as the hippocampus, the , the striatum, or the mammillary bodies are thought to be involved in specific types of memory. For example, the hippocampus is believed to be involved in spatial learning and declarative learning, while the amygdala is thought to be involved in emotional memory. Learning and memory are attributed to changes in neuronal synapses, thought to be mediated by long-term potentiation and long-term depression.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

2. Give the basic mechanisms associated with motivation. (AU Nov 2017)  formulated a sketchy theory of motivation as based on serotonergic co- activation of glutamatergic synapses.  When a stimulus is emotionally strong, there is a release of serotonin in addition to the release of the glutamate that carries the sensory message.  The co-activation of the post-synaptic neuron reinforces the learning of the stimulus and the formation of long-term memory by means of the activation of a signal-transduction pathway from the membrane receptors to transcriptional factors, leading to the production of more of the same membrane receptors and growth factors.  The memory of the pattern of the stimulus becomes embodied in the new formed connections.  Without the serotonergic reinforcement, these connections would not be formed.  Other approaches to monoaminergic reinforcement of glutamatergic synapses have focused on dopamine.  A common target for glutamate and dopamine was found, the protein DARPP-32.  Together with the kinases activated by calcium ion entry through NMDA channels, that protein could help to understand the mechanism of differential learning (learning with motivation) in single cells. 3. Explain the Behaviour of sleep in animals. Sleep in non-human animals refers to how the behavioral and physiological state of sleep, mainly characterized by reversible unconsciousness, non-responsiveness to external stimuli, and motor passivity, appears in different categories of animals. A sleeping cat. The upright ears and the body position suggest the cat is experiencing NREM sleep. In REM sleep, the ears would have been tucked in and the skeletal muscles would have been relaxed due to the functional paralysis signifying REM sleep. Sleep can follow a physiological or behavioral definition. In the physiological sense- sleep is a state characterized by reversible unconsciousness, special brainwave patterns, sporadic eye movement, loss of muscle tone, and a compensatory increase following deprivation of the state. The physiological definition applies well to birds and mammals, In the behavioral sense- sleep is characterized by non-responsiveness to external stimuli, the adoption of a typical posture, and the occupation of a sheltered site, all of which is usually repeated on a 24-hour basis. In the animals (whose brain is not as complex), the behavioral definition is more often used. Sleep in different species  If an arthropod is experimentally kept awake longer than it is used to, then its coming rest period will be prolonged.  In cockroaches that rest period is characterized by the antennae being folded down and by a decreased sensitivity to external stimuli.  In crayfish sleep is characterized by passivity and increased thresholds for sensory stimuli as well as changes in the EEG pattern, markedly differing from the patterns found in crayfish when they are awake. Sleep in fish and reptiles  Some species that always live in shoals or that swim continuously (because of a need for ram ventilation of the gills, for example) are suspected never to sleep.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 Other fishes seem to sleep. For example, zebrafish, tilapia, tench, brown bullhead, and swell shark become motionless and unresponsive at night (or by day, in the case of the swell shark);  Reptiles have been subjected to electrophysiological studies of sleep. That is to say that electrical activity in the brain has been registered when the animals have been asleep.  The EEG pattern in reptilian sleep differs from what is seen in mammals and other higher animals.  In reptiles, sleep time increases following sleep deprivation, and stronger stimuli are needed to awaken the animals when they have been deprived of sleep as compared to when they have slept normally. This suggests that the sleep which follows deprivation is compensatorily deeper. Sleep in birds  There are significant similarities between sleep in birds and sleep in mammals,  Birds compensate for sleep loss in a manner similar to mammals, by deeper or more intense SWS (slow-wave sleep).  Birds have both REM and NREM sleep, and the EEG patterns of both have similarities to those of mammals.  Different birds sleep different amounts, but the associations seen in mammals between sleep and variables such as body mass, brain mass, relative brain mass, basal metabolism and other factors are not found in birds.  The only clear explanatory factor for the variations in sleep amounts for birds of different species is that birds who sleep in environments where they are exposed to predators have less deep sleep than birds sleeping in more protected environments.  A peculiarity that birds share with aquatic mammals, and also with certain species of lizards is the ability for unihemispheric sleep. That is the ability to sleep with one cerebral hemisphere at a time, while the other hemisphere is awake. When only one hemisphere is sleeping, only the contralateral eye will be shut; that is, when the right hemisphere is asleep the left eye will be shut, and vice versa. The distribution of sleep between the two hemispheres and the amount of unihemispheric sleep are determined both by which part of the brain has been the most active during the previous period of wake—that part will sleep the deepest—and it is also determined by the risk of attacks from predators.  Eg., Ducks near the perimeter of the flock are likely to be the ones that first will detect predator attacks. These ducks have significantly more unihemispheric sleep than those who sleep in the middle of the flock, and they react to threatening stimuli seen by the open eye. Sleep in mammals  Different animals sleep different amounts.  Some animals, such as bats, sleep 18–20 hours per day, while others, including giraffes, sleep only 3–4 hours per day.  Mammals have two different stages of sleep: REM and NREM sleep.  An animal's feeding habits are associated with its sleep length.  The daily need for sleep is highest in carnivores, lower in omnivores and lowest in herbivores.  Humans do not sleep unusually much or unusually little compared to other animals, but we sleep less than many other omnivores.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 Many herbivores, eg., Ruminantia (such as cattle), spend much of their wake time in a state of drowsiness, which perhaps could partly explain their relatively low need for sleep.  In herbivores, a direct correlation is apparent between body mass and sleep length; big animals sleep more than smaller ones. This correlation is thought to explain about 25% of the difference in sleep amount between different animals.  Also, the length of a particular sleep cycle is associated with the size of the animal; on average, bigger animals will have sleep cycles of longer durations than smaller animals. Sleep amount is also coupled to factors like basal metabolism, brain mass and relative brain mass.  Mammals born with well-developed regulatory systems, such as the horse and giraffe, tend to have less REM sleep than the species which are less developed at birth, such as cats and rats. This appears to echo the greater need for REM sleep among newborns Sleep in hibernating animals Animals that hibernate are in a state of torpor, differing from sleep. Hibernation markedly reduces the need for sleep, but does not remove it. Hibernating animals end their hibernation a couple of times during the winter so that they can sleep. 4. Explain motivation. Motivation is the driving force which causes us to achieve goals. It is said to be intrinsic or extrinsic. According to various theories, motivation may be rooted in a basic need to minimize physical pain and maximize pleasure, Or it may include specific needs such as eating and resting, or a desired object, goal, state of being, ideal, or it may be attributed to less-apparent reasons such as altruism, selfishness, morality, or avoiding mortality. Intrinsic and extrinsic motivation  Intrinsic motivation refers to motivation that is driven by an interest or enjoyment in the task itself, and exists within the individual rather than relying on any external pressure. Students are likely to be intrinsically motivated if they:  Attribute their educational results to internal factors that they can control (e.g. the amount of effort they put in),  Believe they can be effective agents in reaching desired goals (i.e. the results are not determined by luck),  Are interested in mastering a topic, rather than just rote-learning to achieve good grades. Extrinsic motivation comes from outside of the individual.  Common extrinsic motivations are rewards like money and grades, coercion and threat of punishment.  Competition is in general extrinsic because it encourages the performer to win and beat others, not to enjoy the intrinsic rewards of the activity.  A crowd cheering on the individual and trophies are also extrinsic incentives.

Social psychological research has indicated that extrinsic rewards can lead to over justification and a subsequent reduction in intrinsic motivation. In one study demonstrating this effect, children who expected to be (and were) rewarded with a ribbon and a gold star for drawing pictures spent less time playing with the drawing materials in subsequent observations than children who were assigned to an unexpected reward condition and to children who received no extrinsic reward.

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

5. Explain the theories of Motivation Incentive theory  A reward, tangible or intangible, is presented after the occurrence of an action (i.e. behavior) with the intent to cause the behavior to occur again.  This is done by associating positive meaning to the behavior. Studies show that if the person receives the reward immediately, the effect would be greater, and decreases as duration lengthens.  Repetitive action-reward combination can cause the action to become habit.  Motivation comes from two sources: oneself, and other people. These two sources are called intrinsic motivation and extrinsic motivation, respectively.  A reinforcer is different from reward, in that reinforcement is intended to create a measured increase in the rate of a desirable behavior following the addition of something to the environment.  Incentive theory in psychology, treats motivation and behavior of the individual, as they are influenced by beliefs, such as engaging in activities that are expected to be profitable.  Incentive theory distinguishes itself from other motivation theories, such as drive theory, in the direction of the motivation. Need hierarchy theory  The theory can be summarized as follows:  Human beings have wants and desires which influence their behavior. Only unsatisfied needs influence behavior, satisfied needs do not.  Since needs are many, they are arranged in order of importance, from the basic to the complex.  The person advances to the next level of needs only after the lower level need is at least minimally satisfied.  The further the progress up the hierarchy, the more individuality, humanness and psychological health a person will show. The needs, listed from basic (lowest-earliest) to most complex (highest-latest) are as follows:  Physiology (hunger, thirst, sleep, etc.)  Safety/Security/Shelter/Health  Belongingness/Love/Friendship  Self-esteem/Recognition/Achievement  Self actualization Models of behavior change  Social-cognitive models of behavior change include the constructs of motivation and volition.  Motivation is seen as a process that leads to the forming of behavioral intentions.  Volition is seen as a process that leads from intention to actual behavior.  In other words, motivation and volition refer to goal setting and goal pursuit, respectively. Both processes require self-regulatory efforts. Several self-regulatory constructs are needed to operate in orchestration to attain goals. An example of such a motivational and volitional construct is perceived self-efficacy.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 Self-efficacy is supposed to facilitate the forming of behavioral intentions, the development of action plans, and the initiation of action. It can support the translation of intentions into action. Unconscious motivation  Some psychologists believe that a significant portion of human behavior is energized and directed by unconscious motives.  According to Maslow, "Psychoanalysis has often demonstrated that the relationship between a conscious desire and the ultimate unconscious aim that underlies it need not be at all direct 6. Give a detailed account on neural control of feeding  Any action of an animal directed toward obtaining nutrients. Each species evolves methods of searching for, obtaining, and ingesting food for which it can successfully compete. Some species eat only one type of food, others a variety. Among invertebrates food choices are instinctual, while among vertebrates they are learned.  The living cell depends on a uninterrupted supply of materials for its metabolism. In multicellular animals the body fluids surrounding each cell are the immediate source of nutrients. The contents of these fluids are kept at a relatively constant level in spite of tolls taken by the cells, primarily by mobilization of nutrients stored in the body; in vertebrates, for example, glucose is stored in the liver, fats in the fat tissues, calcium in the bones. These stores, however, will become exhausted unless the animal takes up nutrients from outside. Movements performed for this purpose are termed feeding behaviour.  Cells use nutrients as fuel for energy production (catabolism) and as material for processes of maintenance and growth (anabolism). Multicellular animals derive energy solely from the breakdown of complex organic molecules, mainly carbohydrates and fats. Neural control of feeding The early discovery of discrete nuclei in the brain which - when lesioned - had the dramatic effect of either increasing or decreasing body weight and food intake. These results were seized upon as being possible physiological substrates for the psychological states of hunger and satiety. It is evident from the research findings that two brain areas implicated in the control of eating. The Dual-Control Theory of Feeding Dual-control theory was based on a homeostatic view of hunger and satiety. There are two areas of the brain involved in food intake such as LH and VMH. A decline in glucose activated the lateral hypothalamus (LH), Activity within the LH gave rise to hunger, Hunger motivated the search for and consumption of food, Food was broken down to release glucose and Glucose activated the ventromedial hypothalamus (VMH).

Figure:

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

The idea that the VMH acts as the brain's satiety centre whereas the LH is a hunger centre, was put forward by Eliott Stellar in 1954

Area of hypothalamus Effect of lesioning Effect of stimulating

Ventromedial hypothalamus Increases eating Decreases eating

Lateral hypothalamus Decreases eating Increases eating

Evolutionary adaptations The specialization of organisms towards specific food sources is one of the major causes of evolution of form and function, such as:  mouth parts and teeth, such as in whales, vampire bats, leeches, mosquitos, predatory animals such as felines and fishes, etc  distinct forms of beaks in birds, such as in hawks, woodpeckers, pelicans, hummingbirds, parrots, kingfishers, etc.  specialized claws and other appendages, for apprehending or killing (including fingers in primates)  changes in body colour for facilitating camouflage, disguise, setting up traps for preys, etc.  changes in the digestive system, such as the system of stomachs of herbivores, commensalism and symbiosis Classification By mode of ingestion There are many modes of feeding that animals exhibit, including:  filter feeding - obtaining nutrients from particles suspended in water  deposit feeding - obtaining nutrients from particles suspended in soil  fluid feeding - obtaining nutrients by consuming other organisms' fluids  bulk feeding - obtaining nutrients by eating all of an organism  Ram feeding and Suction feeding - ingesting prey via the fluids around it. 7. Write a detailed account on sleep. Sleep is a naturally recurring state characterized by reduced or lacking consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, but it is more easily reversible than hibernation or coma. Sleep is a heightened anabolic state, accentuating the growth and rejuvenation of the immune, nervous, skeletal and muscular systems. It is observed in all mammals, all birds, and many reptiles, amphibians, and fish.

Sleep will help to conserve energy, but actually decreases metabolism only about 5–10%. Hibernating animals need to sleep despite the hypometabolism seen in hibernation, and in fact they must return from hypothermia to euthermy in order to sleep, making sleeping "energetically expensive Sleep stages.  In mammals and birds, sleep is divided into two broad types: rapid eye movement (REM) and non-rapid eye movement (NREM or non-REM) sleep.

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 Each type has a distinct set of associated physiological, neurological, and psychological features.  The American Academy of Sleep Medicine (AASM) further divides NREM into three stages: N1, N2, and N3, the last of which is also called delta sleep or slow-wave sleep (SWS).  The stages of sleep were first described in 1937 by Alfred Lee Loomis and his coworkers, who separated the different electroencephalography (EEG) features of sleep into five levels (A to E), which represented the spectrum from wakefulness to deep sleep.  Sleep stages and other characteristics of sleep are commonly assessed by polysomnography in a specialized sleep laboratory.  Measurements taken include EEG of brain waves, electrooculography (EOG) of eye movements, and electromyography (EMG) of skeletal muscle activity.  In humans, each sleep cycle lasts from 90 to 110 minutes on average, and each stage may have a distinct physiological function.  This can result in sleep that exhibits loss of consciousness but does not fulfill its physiological functions (i.e., one may still feel tired after apparently sufficient sleep). NREM sleep  Stage N1 refers to the transition of the brain from alpha waves having a frequency of 8– 13 Hz (common in the awake state) to theta waves having a frequency of 4–7 Hz.  This stage is sometimes referred to as somnolence or drowsy sleep.  Sudden twitches and hypnic jerks, also known as positive myoclonus, may be associated with the onset of sleep during N1.  Some people may also experience hypnagogic hallucinations during this stage, which can be troublesome to them. During N1, the subject loses some muscle tone and most conscious awareness of the external environment.  Stage N2 is characterized by sleep spindles ranging from 11–16 Hz (most commonly 12– 14 Hz) and K-complexes. During this stage, muscular activity as measured by EMG decreases, and conscious awareness of the external environment disappears. This stage occupies 45–55% of total sleep in adults.  Stage N3 (deep or slow-wave sleep) is characterized by the presence of a minimum of 20% delta waves ranging from 0.5–2 Hz and having a peak-to-peak amplitude >75 μV. (EEG standards define delta waves to be from 0–4 Hz, but sleep standards in both the original R&K, as well as the new 2007 AASM guidelines have a range of 0.5–2 Hz.) This is the stage in which parasomnias such as night terrors, nocturnal enuresis, sleepwalking, and somniloquy occur. Many illustrations and descriptions still show a stage N3 with 20–50% delta waves and a stage N4 with greater than 50% delta waves; these have been combined as stage N3. REM sleep  Rapid eye movement sleep, or REM sleep, accounts for 20–25% of total sleep time in most human adults.  The criteria for REM sleep include rapid eye movements as well as a rapid low-voltage EEG. Most memorable dreaming occurs in this stage. At least in mammals, a descending muscular atonia is seen. Such paralysis may be necessary to protect organisms from self-damage through physically acting out scenes from the often-vivid dreams that occur during this stage.  Sleep timing is controlled by the circadian clock, sleep-wake homeostasis, and in humans, within certain bounds, willed behavior.

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 The circadian clock—an inner timekeeping, temperature-fluctuating, enzyme-controlling device—works in tandem with adenosine, a neurotransmitter that inhibits many of the bodily processes associated with wakefulness.  Adenosine is created over the course of the day; high levels of adenosine lead to sleepiness.  In diurnal animals, sleepiness occurs as the circadian element causes the release of the hormone melatonin and a gradual decrease in core body temperature. The timing is affected by one's chronotype.  It is the circadian rhythm that determines the ideal timing of a correctly structured and restorative sleep episode. Homeostatic sleep propensity must be balanced against the circadian element for satisfactory sleep. Along with corresponding messages from the circadian clock, this tells the body it needs to sleep. Sleep offset (awakening) is primarily determined by circadian rhythm. A person who regularly awakens at an early hour will generally not be able to sleep much later than his or her normal waking time, even if moderately sleep-deprived. Sleep duration is affected by the gene DEC2. Some people have a mutation of this gene; they sleep two hours less than normal. 8. Describe the control mechanism of hearing with illustrations. (AU Nov 2017)  Hearing (or audition) is the ability to perceive sound by detecting vibrations via an organ such as the ear. It is one of the traditional five senses. The inability to hear is called deafness.  The inner ear includes both the organ of hearing (the cochlea) and a sense organ that is attuned to the effects of both gravity and motion (labyrinth or vestibular apparatus).  The balance portion of the inner ear consists of three semi-circular canals and the vestibule.  The inner ear is encased in the hardest bone of the body. Within this ivory hard bone, there are fluid-filled hollows.  Within the cochlea are three fluid filled spaces: the scala tympani, the scalavestibuli and the scala media.  The eighth cranial nerve comes from the brain stem to enter the inner ear.  When sound strikes the ear drum, the movement is transferred to the footplate of the stapes, which presses it into one of its fluid-filled ducts through the oval window of cochlea.  The fluid inside this duct is moved, flowing against the receptor cells of the Organ of Corti, which fire. These stimulate the spiral ganglion, which sends information through the auditory portion of the eighth cranial nerve to the brain.  Hair cells are also the receptor cells involved in balance, although the hair cells of the auditory and vestibular systems of the ear are not identical.  Vestibular hair cells are stimulated by movement of fluid in the semicircular canals and the utricle and saccule.  Firing of vestibular hair cells stimulates the Vestibular portion of the eighth cranial nerve. In humans and other vertebrates, hearing is performed primarily by the auditory system: vibrations are detected by the ear and transduced into nerve impulses that are perceived by the brain (primarily in the temporal lobe). Like touch, audition requires sensitivity to the movement

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES of molecules in the world outside the organism. Both hearing and touch are types of mechanosensation. 9. List out and explain the diseases of the nervous system A central nervous system disease can affect either the spinal cord (myelopathy) or brain (encephalopathy), both part of the central nervous system. The central nervous system controls behaviors in the human body, so this can be a fatal illness. Encephalitis  Encephalitis is an acute inflammation of the brain. It is usually caused by a foreign substance or a viral infection.  Symptoms for this disease include: headache, neck pain, drowsiness, nausea, and fever. If caused by the West Nile virus it may be lethal to humans, as well as birds and horses.  Encephalitis with meningitis is known as meningoencephalitis.  Symptoms include headache, fever, confusion, drowsiness, and fatigue. More advanced and serious symptoms include seizures or convulsions, tremors, hallucinations, and memory problems. Viral encephalitis  Viral encephalitis can be either due to the direct effects of an acute infection, or as one of the sequelae of a latent infection.  A common cause of encephalitis in humans is herpes simplex virus type I (HSE) which may cause inflammation of the brain.  This can result in death. Others include infection by Flaviviruses such as St. Louis encephalitis or West Nile virus, or Togaviruses such as Eastern equine encephalitis (EEE), Western equine encephalitis (WEE) and Venezuelen equine encephalitis (VEE). Bacterial and other: It can be caused by a bacterial infection, such as bacterial meningitis, spreading directly to the brain (primary encephalitis), or may be a complication of a current infectious disease syphilis (secondary encephalitis). Meningitis  Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges.  The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs.  Meningitis can be life-threatening because of the inflammation's proximity to the brain and spinal cord; and the condition is classified as a medical emergency.  The most common symptoms of meningitis are headache and neck stiffness associated with fever, confusion or altered consciousness, vomiting, and an inability to tolerate light (photophobia) or loud noises (phonophobia).  A lumbar puncture may be used to diagnose or exclude meningitis.  This involves inserting a needle into the spinal canal to extract a sample of cerebrospinal fluid (CSF), the fluid that envelops the brain and spinal cord.  The CSF is then examined in a medical laboratory.  The usual treatment for meningitis is the prompt application of antibiotics and sometimes antiviral drugs. In some situations, corticosteroid drugs can also be used to prevent complications from overactive inflammation. Huntington's Disease

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 Huntington's disease is a rare neurological disorder that is inherited.  Degeneration of neuronal cells in the frontal lobe of the brain occurs.  There is a progressive decline which results in abnormal movements  Huntington's disease affects muscle coordination and leads to cognitive decline and dementia.  The disease is caused by an autosomal dominant mutation on either of an individual's two copies of a gene called Huntingtin.  The mutation of the Huntingtin gene codes for a different form of the protein, whose presence results in gradual damage to specific areas of the brain.  Genetic testing can be performed at any stage of development, even before the onset of symptoms.  The earliest symptoms are a general lack of coordination and an unsteady gait. As the disease advances, uncoordinated, jerky body movements become more apparent, along with a decline in mental abilities and behavioral and psychiatric problems.  Physical abilities are gradually impeded until coordinated movement becomes very difficult, and mental abilities generally decline into dementia.  Complications such as pneumonia, heart disease, and physical injury from falls reduce life expectancy to around twenty years after symptoms begin.  There is no cure for HD, and full-time care is required in the later stages of the disease, but there are emerging treatments to relieve some of its symptoms. Alzheimer’s Disease Alzheimer‘s is a neurodegenerative disease typically found in people over the age of 65 years. It is the most common form of dementia. This incurable, degenerative, and terminal disease was first described by German psychiatrist and neuropathologist Alois Alzheimer in 1906 and was named after him. The earliest observable symptoms are often mistakenly thought to be 'age-related' concerns, or manifestations of stress. In the early stages, the most commonly recognized symptom is inability to acquire new memories, such as difficulty in recalling recently observed facts. When AD is suspected, the diagnosis is usually confirmed with behavioural assessments and cognitive tests, often followed by a brain scan if available. As the disease advances, symptoms include confusion, irritability and aggression, mood swings, language breakdown, long-term memory loss, and the general withdrawal of the sufferer as their senses decline. Gradually, bodily functions are lost, ultimately leading to death. Individual prognosis is difficult to assess, as the duration of the disease varies. AD develops for an indeterminate period of time before becoming fully apparent, and it can progress undiagnosed for years. The mean life expectancy following diagnosis is approximately seven years. Fewer than three percent of individuals live more than fourteen years after diagnosis. Parkinson's  Parkinson‘s affects the motor skills and speech.  Symptoms may include bradykinesia (slow physical movement), muscle rigidity, and tremors. Behavior, thinking, and sensation disorders are non-motor symptoms.  "Parkinson's is a degenerative disorder of the central nervous system that impairs motor skills, cognitive processes, and other functions.

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 The most obvious symptoms are motor-related, including tremor, rigidity, slowness of movement, and postural instability.  Among non-motor symptoms are autonomic dysfunction and sensory and sleep difficulties.  Cognitive and behavioral problems, including dementia, are common in the advanced stages of the disease.  PD usually appears around the age of 60, although there are young-onset cases.  PD is also having a genetic origin. Many risk and protective factors have been investigated, showing an increased risk of PD in those exposed to pesticides; and a reduced risk in smokers.  Symptoms result from insufficient formation and action of dopamine produced in the dopaminergic neurons of the midbrain (specifically the ).  Pathologically the disease is characterized by the accumulation of alpha-synuclein protein forming inclusions called Lewy bodies.  Such pathology can only be demonstrated at autopsy so diagnosis is mainly clinical (based on symptoms).  Some tests such as neuroimaging techniques can also aid in diagnosis.  Current treatments are effective at managing the early motor symptoms of the disease, mainly through the use of levodopa and dopamine agonists.  As the disease advances, however, the continued use of medications leads to a second stage in which the patient develops motor complications called dyskinesias.  Medications to treat other symptoms of PD also exist.  Diet and some forms of rehabilitation have shown some effectiveness at mitigating symptoms, and surgery and deep brain stimulation may be used to reduce motor symptoms in the most extreme cases. Multiple sclerosis  Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease, meaning that the myelin sheath of neurons is damaged.  Symptoms of MS include: visual and sensation problems, muscle weakness, and depression.  Multiple sclerosis (abbreviated MS, also known as disseminated sclerosis or encephalomyelitis disseminata) is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms. Disease onset usually occurs in young adults, and it is more common in females.  MS affects the ability of nerve cells in the brain and spinal cord to communicate with each other.  Nerve cells communicate by sending electrical signals called action potentials down long fibers called axons, which are wrapped in an insulating substance called myelin.  In MS, the body's own immune system attacks and damages the myelin.  When myelin is lost, the axons can no longer effectively conduct signals.  The name multiple sclerosis refers to scars (scleroses—better known as plaques or lesions) particularly in the white matter of the brain and spinal cord, which is mainly composed of myelin.

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 Almost any neurological symptom can appear with the disease, and often progresses to physical and cognitive disability.  MS takes several forms, with new symptoms occurring either in discrete attacks (relapsing forms) or slowly accumulating over time (progressive forms).  Between attacks, symptoms may go away completely, but permanent neurological problems often occur, especially as the disease advances.  There is no known cure for MS.  Treatments attempt to return function after an attack, prevent new attacks, and prevent disability.  MS medications can have adverse effects or be poorly tolerated, and many patients pursue alternative treatments, despite the lack of supporting scientific study.  The prognosis is difficult to predict; it depends on the subtype of the disease, the individual patient's disease characteristics, the initial symptoms and the degree of disability the person experiences as time advances.  Life expectancy of patients is 5 to 10 years lower than that of the unaffected population Trauma or Traumatic brain injury (TBI)  Any type of traumatic brain injury (TBI) or injury done to the spinal cord can result in a wide spectrum of disabilities in a person.  Depending on the section of the brain or spinal cord that suffers the trauma the outcome may be anticipated.  Traumatic brain injury (TBI), also known as intracranial injury, occurs when an external force traumatically injures the brain.  TBI can be classified based on severity, mechanism (closed or penetrating head injury), or other features (e.g. occurring in a specific location or over a widespread area).  Head injury usually refers to TBI, but is a broader category because it can involve damage to structures other than the brain, such as the scalp and skull.  TBI is a major cause of death and disability worldwide, especially in children and young adults.  Causes include falls, vehicle accidents, and violence.  Prevention measures include use of technology to protect those who are in accidents, such as seat belts and sports or motorcycle helmets, as well as efforts to reduce the number of accidents, such as safety programs and enforcement of traffic laws.  Brain trauma can be caused by a direct impact or by acceleration alone.  In addition to the damage caused at the moment of injury, brain trauma causes secondary injury, a variety of events that take place in the minutes and days following the injury.  These processes, which include alterations in cerebral blood flow and the pressure within the skull, contribute to the damage from the initial injury.  TBI can cause a host of physical, cognitive, emotional, and behavioral effects, and outcome can range from complete recovery to permanent disability or death.  The 20th century saw critical developments in diagnosis and treatment which decreased death rates and improved outcome. These include imaging techniques such as computed tomography and magnetic resonance imaging.

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

 Depending on the injury, treatment required may be minimal or may include interventions such as medications and emergency surgery. Physical therapy, speech therapy, recreation therapy, and occupational therapy may be employed for rehabilitation. Degeneration Degenerative spinal disorders involve a loss of function in the spine. Pressure on the spinal cord and nerves may be associated with herniation or disc displacement. Brain degeneration also causes central nervous system diseases. Tumors  A tumor is an abnormal growth of body tissue.  If benign, tumors can be non-cancerous, but if they are malignant, they are cancerous.  In general, they appear when there is a problem with cellular division. Problems with the body‘s immune system can lead to tumors. Autoimmune disorders An autoimmune disorder is a condition where the immune system attacks and destroys healthy body tissue. This is caused by harmful substances, called antigens. Autoimmune nervous system diseases Guillain-Barre syndrome is a neurological disorder in which the body's immune system attacks part of the peripheral nervous system. Symptoms of Guillain-Barré syndrome vary from person to person and may be mild or severe. Most often, the first prominent symptom is weakness, and most often the weakness is felt in both legs. The weakness is accompanied by decreased feeling (paresthesia). Lambert-Eaton myasthenic syndrome (LEMS) is an uncommon neuromuscular disorder characterized by weakness in muscles of the upper arms and upper legs, and less commonly, muscles of the neck, speech, swallowing, breathing and eye movement. Lambert-Eaton myasthenic syndrome (LEMS) is caused by a disruption of electrical impulses between these nerve and muscle cells. Multiple sclerosis (MS) is a demyelinating disease, a non-contagious chronic autoimmune disorder of the central nervous system which can present with a variety of neurological symptoms occurring in attacks or slowly progressing over time. Multiple sclerosis (MS) can be thought of as an inflammatory process involving different areas of the central nervous system (CNS) at various points in time Myasthenia gravis is an autoimmune disease that affects the transmission of signals from nerves to muscles. Myasthenia gravis is caused by a defect in the transmission of nerve impulses to muscles. It occurs when normal communication between the nerve and muscle is interrupted at the neuromuscular junction - the place where nerve cells connect with the muscles they control. Transverse myelitis (TM) is an uncommon neurological syndrome caused by inflammation (a protective response which includes swelling, pain, heat, and redness) of the spinal cord, characterized by weakness, back pain, and bowel and bladder problems. It affects one to five persons per million. Acute transverse myelitis is a neurological disorder caused by inflammation of the spinal cord, which damages or destroys myelin, the fatty insulating substance that covers nerve cells fibers. Progressive multifocal leukoencephalopathy is an advancing viral inflammation of the white matter of the brain. Immunosuppressed people are more susceptible to this disorder than the general population. Evidence of the disease may be a person´s recent loss of coordination and weakness, progressing to a loss of language, visual problems and headaches

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE

VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE DEPARTMENT OF BIOTECHNOLOGY BT 6018- NEUROBIOLOGY AND COGNITIVE SCIENCES

Stroke  A stroke is an interruption of the blood supply to the brain. This can happen when a blood vessel is blocked by a blood clot or when a blood vessel ruptures, causing blood to leak to the brain. If the brain cannot get enough oxygen and blood, brain cells can die, leading to permanent damage.  A stroke, previously known medically as a cerebrovascular accident (CVA), is the rapidly developing loss of brain function(s) due to disturbance in the blood supply to the brain. This can be due to ischemia (lack of blood flow) caused by blockage (thrombosis, arterial embolism), or a hemorrhage (leakage of blood).  As a result, the affected area of the brain is unable to function, leading to inability to move one or more limbs on one side of the body, inability to understand or formulate speech, or an inability to see one side of the visual field.  A stroke is a medical emergency and can cause permanent neurological damage, complications, and lead to death.  Risk factors for stroke include advanced age, hypertension (high blood pressure), previous stroke or transient ischemic attack (TIA), diabetes, high cholesterol, cigarette smoking and atrial fibrillation.  High blood pressure is the most important modifiable risk factor of stroke  An ischemic stroke is occasionally treated in a hospital with thrombolysis (also known as a ―clot buster‖), and some hemorrhagic strokes benefit from neurosurgery.  Treatment to recover any lost function is stroke rehabilitation, ideally in a stroke unit and involving health professions such as speech and language therapy, physical therapy and occupational therapy.  Prevention of recurrence may involve the administration of antiplatelet drugs such as aspirin and dipyridamole, control and reduction of hypertension, and the use of statins. Selected patients may benefit from carotid endarterectomy and the use of anticoagulants.

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VEL TECH HIGH TECHDr. RANGARAJAN Dr. SAKUNTHALA ENGINEERING COLLEGE