The

• A network of billions of nerve cells linked together in a highly organized fashion to form the rapid control center of the body. • Functions include: – Integrating center for homeostasis, movement, and almost all other body functions. – The mysterious source of those traits that we think of as setting humans apart from animals

Basic Functions of the Nervous System

1. Sensation • Monitors changes/events occurring in and outside the body. Such changes are known as stimuli and the cells that monitor them are receptors. 2. Integration • The parallel processing and interpretation of sensory information to determine the appropriate response 3. Reaction • Motor output. – The activation of muscles or glands (typically via the release of neurotransmitters (NTs))

Organization of the Nervous System

• 2 big initial divisions: 1. • The brain + the spinal cord – The center of integration and control 2. Peripheral Nervous System • The nervous system outside of the brain and spinal cord • Consists of: – 31 Spinal nerves » Carry info to and from the spinal cord – 12 Cranial nerves » Carry info to and from the brain Peripheral Nervous System

• Responsible for communication btwn the CNS and the rest of the body. • Can be divided into: – Sensory Division • Afferent division – Conducts impulses from receptors to the CNS – Informs the CNS of the state of the body interior and exterior – fibers can be somatic (from skin, skeletal muscles or joints) or visceral (from organs w/i the ventral body cavity) – Motor Division • Efferent division – Conducts impulses from CNS to effectors (muscles/glands) – fibers Motor Efferent Division

• Can be divided further: – Somatic nervous system • VOLUNTARY (generally) • Somatic nerve fibers that conduct impulses from the CNS to skeletal muscles – Autonomic nervous system • INVOLUNTARY (generally) • Conducts impulses from the CNS to smooth muscle, cardiac muscle, and glands. Autonomic Nervous System

• Can be divided into: – Sympathetic Nervous System • “Fight or Flight” – Parasympathetic Nervous System • “Rest and Digest”

These 2 systems are antagonistic. Typically, we balance these 2 to keep ourselves in a state of dynamic balance. We’ll go further into the difference btwn these 2 later!

1.

• Highly cellular – How does this compare to the other 3 tissue types? • 2 cell types 1. 2. • Functional, signal conducting cells 2. Neuroglia • Supporting cells Neuroglia

• Outnumber neurons by about 10 to 1 (the guy on the right had an inordinate amount of them). • 6 types of supporting cells – 4 are found in the CNS: 1. • Star-shaped, abundant, and versatile • Guide the migration of developing neurons • Act as K+ and NT buffers • Involved in the formation of the blood brain barrier • Function in nutrient transfer

Neuroglia

2. • Specialized immune cells that act as the macrophages of the CNS • Why is it important for the CNS to have its own army of immune cells? 3. Ependymal Cells • Low columnar epithelial-esque cells that line the ventricles of the brain and the central canal of the spinal cord • Some are ciliated which facilitates the movement of cerebrospinal fluid

Neuroglia

4. • Produce the sheath which provides the electrical insulation for certain neurons in the CNS

Neuroglia

• 2 types of in the PNS 1. Satellite cells • Surround clusters of neuronal cell bodies in the PNS • Unknown function 2. Schwann cells • Form myelin sheaths around the larger nerve fibers in the PNS. • Vital to neuronal regeneration

• The functional and structural unit Neurons of the nervous system • Specialized to conduct information from one part of the body to another • There are many, many different types of neurons but most have certain structural and functional characteristics in common:

- Cell body () - One or more specialized, slender processes (/) - An input region (dendrites/soma) - A conducting component () - A secretory (output) region () Soma

• Contains nucleus plus most normal organelles. • Biosynthetic center of the . • Contains a very active and developed rough endoplasmic reticulum which is responsible for the synthesis of ______. In the soma above, notice the small black circle. It is the nucleolus, the site – The neuronal rough ER is of ribosome synthesis. The light referred to as the . circular area around it is the nucleus. • Contains many bundles of The mottled dark areas found protein filaments (neurofibrils) throughout the cytoplasm are the Nissl which help maintain the shape, substance. structure, and integrity of the cell. Neuronal Processes

• Armlike extensions emanating from every neuron. • The CNS consists of both somata and processes whereas the bulk of the PNS consists of processes. • Tracts = Bundles of processes in the CNS (red arrow) Nerves = Bundles of processes in the PNS • 2 types of processes that differ in structure and function: – Dendrites and Axons • Dendrites are thin, branched processes whose main function is to receive incoming signals. • They effectively increase the surface area of a neuron to increase its ability to communicate with other neurons. • Small, mushroom-shaped dendritic spines further increase the SA • Convey info towards the soma thru the use of graded potentials – which are somewhat similar to action potentials.

Notice the multiple processes extending from the neuron on the right. Also notice the multiple dark circular dots in the slide. They’re not neurons, so they must be… • Most neurons have a single axon – a long (up to 1m) process designed to convey info away from the cell body. • Originates from a special region of the cell body called the . • Transmit APs from the soma toward the end of the axon where they cause NT release. • Often branch sparsely, forming collaterals. • Each collateral may split into telodendria which end in a synaptic knob, which contains synaptic vesicles – membranous bags of NTs. Axons

• = axon plasma membrane. • Surrounded by a myelin sheath, a wrapping of lipid which: – Protects the axon and electrically isolates it – Increases the rate of AP transmission • The myelin sheath is made by ______in the CNS and by ______in the PNS. • This wrapping is never complete. Interspersed along the axon are gaps where there is no myelin – these are nodes of Ranvier. • In the PNS, the exterior of the surrounding an axon is the neurilemma Myelination in the CNS

Myelination in the PNS • A bundle of processes in the PNS is a nerve. • Within a nerve, each axon is surrounded by an (too small to see on the photomicrograph) – a layer of loose CT.

• Groups of fibers are bound together into bundles (fascicles) by a (red arrow). • All the fascicles of a nerve are enclosed by a (black arrow). Action Potential Conduction

• If an AP is generated at the axon hillock, it will travel all the way down to the synaptic knob. • The manner in which it travels depends on whether the neuron is myelinated or unmyelinated. • Unmyelinated neurons undergo the continuous conduction of an AP whereas myelinated neurons undergo saltatory conduction of an AP. Continuous Conduction • Occurs in unmyelinated axons. • In this situation, the wave of de- and repolarization simply travels from one patch of membrane to the next adjacent patch. • APs moved in this fashion along the sarcolemma of a muscle fiber as well. • Analogous to dominoes falling. Saltatory Conduction

• Occurs in myelinated axons. • Saltare is a Latin word meaning “to leap.” • Recall that the myelin sheath is not completed. There exist myelin free regions along the axon, the nodes of Ranvier.

Types of Nerve Fibers

1. Group A – Axons of the somatic sensory neurons and motor neurons serving the skin, skeletal muscles, and joints. – Large diameters and thick myelin sheaths. • How does this influence their AP conduction? 2. Group B – Type B are lightly myelinated and of intermediate diameter. 3. Group C – Type C are unmyelinated and have the smallest diameter. – Autonomic nervous system fibers serving the visceral organs, visceral sensory fibers, and small somatic sensory fibers are Type B and Type C fibers.

Synaptic Transmission • An AP reaches the axon terminal of the presynaptic cell and causes V-gated Ca2+ channels to open. • Ca2+ rushes in, binds to regulatory proteins & initiates NT exocytosis. • NTs diffuse across the synaptic cleft and then bind to receptors on the postsynaptic membrane and initiate some sort of response on the postsynaptic cell. Development of the Central Nervous System

 an ongoing process, through adolescence and maybe even adult hood ?  the nervous system is “plastic”

 Experience plays a key role

 Dire consequences when something goes wrong - “teratogens”

- Drugs of abuse, industrial chemicals, caffeine?, household chemicals

Stages of Development

Phase Approximate Age Highlight

Prenatal Conception - birth Rapid physical growth Infancy Birth - 2 yrs Motor development Childhood 2 - 12 yrs Abstract reasoning Adolescence 13 - 20 yrs Identity creation, “Judgement”

Directly related to maturation of the “Prefrontal Cortex” Phases of Prenatal Development • Ovum + sperm – zygote

• Once zygote implants in uterus – embryo

• Week 8 until birth – fetus

The University of South Wales, Dr. Mark Hill At about 18 days after conception the embryo begins to implant in the uterine wall.

a. Consists of 3 layers of cells: endoderm, mesoderm, and ectoderm. Thickening of the ectoderm leads to the development of the neural plate

b. The neural groove begins to develop at 20 days. c. At 22 days the neural groove closes along the length of the embryo making the neural tube. d. A few days later 4 major divisions of the brain are observable – the telencephalon, diencephalon, mesencephalon, and rhombencephalon. Phases of brain development

– Neural plate induction

– Neural proliferation

– Migration & Aggregation

– Axon growth & formation

– Cell death & Synapse rearrangement

Induction of the Neural Plate

• 2-3 weeks after conception

• A patch of tissue on the dorsal surface of the embryo that will become the nervous system

• Development induced by chemical signals

“growth factors”: several chemicals produced in developing and mature brain that stimulate neuron development and help neurons respond to injury Neural Plate

 Totipotent (zygote) – Fertilized ovum has ability to divide and produce all cells of the body (brain, kidney, liver, skin, bone etc.)  Can produce a whole animal

 Pluripotent: 5 days after fertilization = blastocyst forms, some of these cells are embryonic“stem cells”. Can be taken and differentiated into any organ ?  With the development of the neural tube, cells become multipotent –  able to develop into any type of mature nervous system cell

Phases of brain development

– Neural plate induction

– Neural proliferation

– Migration & Aggregation

– Axon growth & Synapse formation

– Cell death & Synapse rearrangement

2. Mitosis/Proliferation

Proliferation – Generation of new cells

3 swellings at the anterior end in humans will become the forebrain, midbrain, and hindbrain

•Occurs in ventricular zone •Rate can be 250,000/min •After mitosis “daughter” cells become “fixed” post mitotic 3. Migration: slow movement to the “right place”

Only a soma and immature axon at this point -undifferentiated at start of migration. Differentiation begins as neurons migrate. They develop neurotransmitter making ability, action potential 3. Migration Radial Glia

Radial glial cells act as guide wires for the migration of neurons Migrating cells are immature, lacking dendrites Cells that are done migrating align themselves with others cells and form structures (Aggregation)

Growth Cones: tips of axons on migrating, immature neurons

Growth cones crawl forward as they elaborate the axons training behind them. Their extension is controlled by chemical cues in their outside environment that ultimately direct them toward their appropriate targets. Chemoattractants Vs Chemorepellants

5 Phases of Neurodevelopment

– Neural plate induction

– Neural proliferation

– Migration & Aggregation

– Axon growth & Synapse formation

– Cell death & Synapse rearrangement

4. Axon Growth/Synaptogenesis

 Once migration is complete and structures have formed (aggregation), axons and dendrites begin to grow to their “mature” size/shape.

 Axons (with growth cones on end) and dendrites form a synapse with other neurons or tissue (e.g. muscle)

Growth cones and chemo-attractants are critical for this.

Synaptogenesis

• Formation of new

• Depends on the presence of glial cells – especially astrocytes

• Chemical signal exchange between pre- and postsynaptic neurons is needed 5 Phases of Neurodevelopment

– Neural plate induction

– Neural proliferation

– Migration & Aggregation

– Axon growth & Synapse formation

– Cell death & Synapse rearrangement

5. Neuronal Death

 Between 40-75% neurons made, will die after migration – death is normal and necessary !!

 Neurons die due to failure to compete for chemicals provided by targets

Neurotrophins – promote growth and survival guide axons stimulate synaptogenesis

Synaptic rearrangment

Release and Neurons receiving Axonal processes uptake of insufficient complete for limited neurotrophic neurotropic factor die neurotrophic factor factors Synaptic rearrangment, cont’d: Myelination

Time after synaptogenesis Postnatal Cerebral Development Human Infants

• Postnatal growth is a consequence of – Synaptogenesis – Increased dendritic branches – Myelination (prefrontal cortex continues into adolescence)

• Overproduction of synapses may underlie the greater “plasticity” of the young brain

• Young brain more able to recover function after injury, as compared to older brain

Early Studies of Experience and Brain Development

• Early visual deprivation  – fewer synapses and dendritic spines in visual cortex – deficits in depth and pattern vision

• “Enriched” environment  – thicker cortices – greater dendritic development – more synapses per neuron

Development of the Prefrontal Cortex

• Believed to underlie age-related changes in cognitive function, judgement, decision- making

• No single theory explains the function of this area

• Prefrontal cortex plays a role in working memory, planning and carrying out sequences of actions, and inhibiting inappropriate responses Where is your Prefrontal Cortex ? Postnatal Cerebral Development: Adolescence • The prefrontal lobe is the last to fully develop

• http://www.youtube.com/watch?v=4- 9sjvitKWA Neuroplasticity in Adults ?

• Mature brain changes and adapts

• Neurogenesis (birth of new neurons) – seen only in olfactory bulb and hippocampus of adult mammals

– Not clear if this is critical for “normal” adult behavior Effects of Experience on the Reorganization of the Adult Cortex Skill training leads to reorganization of motor cortex

Adult musicians who play instruments have an enlarged representation of the hand in somatosensory cortex

Reorganization is synaptogenesis or pruning of unused synapses…

Neurodevelopmental Disorders

• Autism Spectrum Disorders – 1/91 live births in U.S.)

• Fetal Alcohol Spectrum Disorders – (1/100 live births in North America ?) Autism

• http://health.yahoo.com/nervous-videos/what-is-autism/healthination-- HNB10051_autism_1.html

• 3 core symptoms: – Reduced ability to communicate – Reduced capacity for social interaction – Preoccupation with a single subject or activity

• Heterogenous – level of brain damage and dysfunction varies (Autism Spectrum Disorder) – Probably no single cause

Autism

• Most have some abilities preserved

. Savants – intellectually handicapped individuals who display specific cognitive or artistic abilities ~1/10 autistic individuals display savant abilities

Neural Basis of Autism

• Genetic basis – Siblings of the autistic have a 5% chance of being autistic – 60% concordance rate for monozygotic twins

• Several genes interacting with the environment

Fetal Alcohol Spectrum Disorders 50+% of women who could become pregnant are drinking

2% of women drink significantly during pregnancy, 10% drink some

Glass of wine, bottle of beer, shot of liquor are equal approximately 0.5 oz absolute alcohol

Fetal brain damage occurs at regular doses of 1-2 oz/day (2-4 drinks)

Source: National Institute on Alcohol Abuse and Alcoholism Symptoms of FASD

Infant: Problems with sleep, feeding, milestones, muscle tone, sensory information processing

Child: Hyperactive, poorly coordinated, learning delays

Adolescent/Adult: poor judgment, attention, problems with arithmetic, memory, abstraction, frustration/anger Neural Basis of Fetal Alcohol Spectrum Disorders When is alcohol exposure most dangerous ??? Neural Basis of Fetal Alcohol Spectrum Disorders

Alcohol inhibits all stages of brain development, except neuronal death, which it promotes.

Brain damage resulting from prenatal alcohol

Brain of baby with Brain of baby with heavy no exposure to alcohol prenatal exposure to alcohol

Photo courtesy of Sterling Clarren, MD