Axon (Nerve Fiber)—

Home , Axolemma, Axon hillock, Axon terminal, Bipolar neuron, Chemical synapse, Neurilemma

Chapter 12 *Lecture PowerPoint

Nervous Tissue

*See separate FlexArt PowerPoint slides for all figures and tables preinserted into PowerPoint without notes.

• The nervous system is one of great complexity • Nervous system is the foundation of our conscious experience, personality, and behavior • Neurobiology combines the behavioral and life sciences

11-2 Overview of the Nervous System

• Expected Learning Outcomes – Describe the overall function of the nervous system. – Describe its major anatomical and functional subdivisions.

11-3 Overview of the Nervous System

• Endocrine and nervous systems maintain internal coordination – Endocrine system: communicates by means of chemical messengers (hormones) secreted into to the blood – Nervous system: employs electrical and chemical means to send messages from cell to cell

12-4 Overview of the Nervous System

• Nervous system carries out its task in three basic steps • Sense organs receive information about changes in the body and the external environment, and transmit coded messages to the spinal cord and the brain • Brain and spinal cord process this information, relate it to past experiences, and determine what response is appropriate to the circumstances • Brain and spinal cord issue commands to muscles and gland cells to carry out such a response

12-5 Overview of the Nervous System

• Nervous system has two major anatomical subdivisions – Central nervous system (CNS) • Brain and spinal cord enclosed in bony coverings • Enclosed by cranium and vertebral column

– Peripheral nervous system (PNS) • All the nervous system except the brain and spinal cord; composed of nerves and ganglia • Nerve—a bundle of nerve fibers (axons) wrapped in fibrous connective tissue • Ganglion—a knotlike swelling in a nerve where neuron cell bodies are concentrated

12-6 Overview of the Nervous System

• Peripheral nervous system has two major functional subdivisions – Sensory (afferent) division: carries sensory signals from various receptors to the CNS • Informs the CNS of stimuli within or around the body

– Somatic sensory division: carries signals from receptors in the skin, muscles, bones, and joints

– Visceral sensory division: carries signals from the viscera of the thoracic and abdominal cavities • Heart, lungs, stomach, and urinary bladder

12-7 Overview of the Nervous System

• Motor (efferent) division—carries signals from the CNS to gland and muscle cells that carry out the body’s response – Effectors: cells and organs that respond to commands from the CNS – Somatic motor division: carries signals to skeletal muscles • Output produces muscular contraction as well as somatic reflexes—involuntary muscle contractions

12-8 Overview of the Nervous System

• Visceral motor division (autonomic nervous system) – Carries signals to glands, cardiac muscle, and smooth muscle – Involuntary, and responses of this system and its receptors are visceral reflexes – Sympathetic division • Tends to arouse body for action • Accelerating heart beat and respiration, while inhibiting digestive and urinary systems – Parasympathetic division • Tends to have calming effect • Slows heart rate and breathing • Stimulates digestive and urinary systems

12-9 Subdivisions of the Nervous System

Spinal cord Nerves

Ganglia

Central nervous system Peripheral nervous system

Spinal Sensory Motor Brain cord division division

Visceral Somatic Visceral Somatic sensory sensory motor motor division division division division

Figure 12.2 Sympathetic Parasympathetic division division 12-11 Properties of Neurons

• Expected Learning Outcomes – Describe three functional properties found in all neurons. – Define the three most basic functional categories of neurons. – Identify the parts of a neuron. – Explain how neurons transport materials between the cell body and tips of the axon.

12-12 Universal Properties

• Excitability (irritability) – Respond to environmental changes called stimuli • Conductivity – Neurons respond to stimuli by producing electrical signals that are quickly conducted to other cells at distant locations • Secretion – When electrical signal reaches end of nerve fiber, a chemical neurotransmitter is secreted that crosses the gap and stimulates the next cell

12-13 Functional Classes

• Three general classes of neurons (sensory, interneuron, motor) based on function

• Sensory (afferent) neurons – Specialized to detect stimuli – Transmit information about them to the CNS • Begin in almost every organ in the body and end in CNS • Afferent—conducting signals toward CNS

12-14 Functional Classes

• Three general classes of neurons (cont.)

• Interneurons (association neurons) – Lie entirely within the CNS – Receive signals from many neurons and carry out the integrative function • Process, store, and retrieve information and “make decisions” that determine how the body will respond to stimuli – 90% of all neurons are interneurons – Lie between and interconnect the incoming sensory pathways and the outgoing motor pathways of the CNS

12-15

Functional Classes

• Three general classes of neurons (cont.)

• Motor (efferent) neuron – Send signals out to muscles and gland cells (the effectors) • Motor because most of them lead to muscles • Efferent neurons conduct signals away from the CNS

12-16 Classes of Neurons

Peripheral nervous system Central nervous system

1 Sensory (afferent) neurons conduct signals from receptors to the CNS.

2 Inter neurons 3 Motor (efferent) (association neurons conduct neurons) are signals from the CNS confined to to effectors such as the CNS. muscles and glands.

• Soma—the control center of the Dendrites neuron

– Also called neurosoma, cell Soma Nucleus body, or perikaryon Nucleolus

– Has a single, centrally located Trigger zone: Axon hillock nucleus with large nucleolus Initial segment

– Cytoplasm contains Axon collateral Axon mitochondria, lysosomes, a Golgi

complex, numerous inclusions, Direction of signal transmission and extensive rough endoplasmic Internodes

reticulum and cytoskeleton Node of Ranvier

– Cytoskeleton consists of dense Myelin sheath mesh of microtubules and Schwann cell neurofibrils (bundles of actin

filaments) Terminal arborization • Compartmentalizes rough ER

into dark-staining Nissl bodies Synaptic knobs

(a) 12-18 Figure 12.4a Structure of a Neuron Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • Soma—the control center of the Dendrites neuron (cont.) Soma Nucleus – No centrioles: no further cell Nucleolus division Trigger zone: Axon hillock – Inclusions: glycogen granules, Initial segment lipid droplets, melanin, and Axon collateral lipofuscin (golden brown pigment Axon produced when lysosomes digest Direction of worn-out organelles) signal transmission • Lipofuscin accumulates with age Internodes • Wear-and-tear granules Node of Ranvier Myelin sheath • Most abundant in old neurons Schwann cell

Terminal arborization

Synaptic knobs

Dendrites • Dendrites—vast number of

branches coming from a few Soma Nucleus thick branches from the soma Nucleolus

Trigger zone: – Resemble bare branches of a Axon hillock tree in winter Initial segment

Axon collateral – Primary site for receiving Axon signals from other neurons Direction of – The more dendrites the signal transmission neuron has, the more Internodes information it can receive and Node of Ranvier Myelin sheath incorporate into decision Schwann cell making – Provide precise pathway for Terminal the reception and processing arborization

of neural information Synaptic knobs

Dendrites • Axon (nerve fiber)—

originates from a mound on Soma Nucleus one side of the soma called Nucleolus

the axon hillock Trigger zone: Axon hillock – Cylindrical, relatively Initial segment unbranched for most of its Axon collateral Axon length

Direction of • Axon collaterals—branches signal transmission of axon Internodes – Branch extensively on distal Node of Ranvier Myelin sheath

end Schwann cell – Specialized for rapid conduction of nerve signals to Terminal points remote to the soma arborization

Synaptic knobs

(a) 12-21 Figure 12.4a Structure of a Neuron

• Axon (nerve fiber) (cont.) Dendrites – Axoplasm: cytoplasm of axon

Soma – Axolemma: plasma membrane Nucleus Nucleolus of axon

Trigger zone: – Only one axon per neuron Axon hillock Initial segment – Schwann cells and myelin Axon collateral sheath enclose axon Axon

– Distal end, axon has terminal Direction of signal transmission

arborization: extensive complex Internodes

of fine branches Node of Ranvier

• Synaptic knob (terminal Myelin sheath button)—little swelling that forms Schwann cell a junction (synapse) with the next cell Terminal • Contains synaptic vesicles full arborization of neurotransmitter Synaptic knobs

– Most common Dendrites

– Most neurons in the brain and spinal cord Axon

Multipolar neurons • Bipolar neuron

– One axon and one dendrite Dendrites – Olfactory cells, retina, inner ear

• Unipolar neuron Axon

– Single process leading away from the Bipolar neurons soma Dendrites – Sensory from skin and organs to spinal cord Axon Unipolar neuron • Anaxonic neuron Dendrites – Many dendrites but no axon – Help in visual processes Anaxonic neuron Figure 12.5 12-23 Axonal Transport

• Many proteins made in soma must be transported to axon and axon terminal – To repair axolemma, serve as gated ion channel proteins, as enzymes or neurotransmitters

• Axonal transport—two-way passage of proteins, organelles, and other material along an axon – Anterograde transport: movement down the axon away from soma – Retrograde transport: movement up the axon toward the soma

• Microtubules guide materials along axon – Motor proteins (kinesin and dynein) carry materials “on their backs” while they “crawl” along microtubules • Kinesin—motor proteins in anterograde transport • Dynein—motor proteins in retrograde transport 12-24 Axonal Transport

• Fast axonal transport—occurs at a rate of 20 to 400 mm/day – Fast anterograde transport (up to 400 mm/day) • Organelles, enzymes, synaptic vesicles, and small molecules – Fast retrograde transport • For recycled materials and pathogens—rabies, herpes simplex, tetanus, polio viruses – Delay between infection and symptoms is time needed for transport up the axon • Slow axonal transport or axoplasmic flow—0.5 to 10 mm/day – Always anterograde – Moves enzymes, cytoskeletal components, and new axoplasm down the axon during repair and regeneration of damaged axons – Damaged nerve fibers regenerate at a speed governed by slow axonal transport 12-25 Supportive Cells (Neuroglia)

• Expected Learning Outcomes – Name the six types of cells that aid neurons and state their respective functions. – Describe the myelin sheath that is found around certain nerve fibers and explain its importance. – Describe the relationship of unmyelinated nerve fibers to their supportive cells. – Explain how damaged nerve fibers regenerate.

12-26 Supportive Cells (Neuroglia)

• About 1 trillion (1012) neurons in the nervous system • Neuroglia outnumber the neurons by as much as 50 to 1 • Neuroglia or glial cells – Support and protect the neurons – Bind neurons together and form framework for nervous tissue – In fetus, guide migrating neurons to their destination – If mature neuron is not in synaptic contact with another neuron it is covered by glial cells • Prevents neurons from touching each other • Gives precision to conduction pathways 12-27 Types of Neuroglia

• Four types occur only in CNS – Oligodendrocytes • Form myelin sheaths in CNS • Each armlike process wraps around a nerve fiber forming an insulating layer that speeds up signal conduction – Ependymal cells • Line internal cavities of the brain • Cuboidal epithelium with cilia on apical surface • Secretes and circulates cerebrospinal fluid (CSF) – Clear liquid that bathes the CNS

12-28 Types of Neuroglia

• Four types occur only in CNS (cont.) – Microglia • Small, wandering macrophages formed white blood cell called monocytes • Thought to perform a complete checkup on the brain tissue several times a day • Wander in search of cellular debris to phagocytize

12-29 Types of Neuroglia

• Four types occur only in CNS (cont.) – Astrocytes • Most abundant glial cell in CNS • Cover entire brain surface and most nonsynaptic regions of the neurons in the gray matter of the CNS • Diverse functions – Form a supportive framework of nervous tissue – Have extensions (perivascular feet) that contact blood capillaries that stimulate them to form a tight seal called the blood–brain barrier – Convert blood glucose to lactate and supply this to the neurons for nourishment

12-30 Types of Neuroglia

Cont. • Nerve growth factors secreted by astrocytes promote neuron growth and synapse formation • Communicate electrically with neurons and may influence synaptic signaling • Regulate chemical composition of tissue fluid by absorbing excess neurotransmitters and ions • Astrocytosis or sclerosis—when neuron is damaged, astrocytes form hardened scar tissue and fill space formerly occupied by the neuron

12-31 Types of Neuroglia

• Two types occur only in PNS

– Schwann cells • Envelope nerve fibers in PNS • Wind repeatedly around a nerve fiber • Produce a myelin sheath similar to the ones produced by oligodendrocytes in CNS • Assist in the regeneration of damaged fibers

– Satellite cells • Surround the neurosomas in ganglia of the PNS • Provide electrical insulation around the soma • Regulate the chemical environment of the neurons

12-32 Neuroglial Cells of CNS

Capillary Neurons

Astrocyte Oligodendrocyte

Perivascular feet Myelinated axon

Ependymal cell Myelin (cut)

Cerebrospinal fluid Microglia

Figure 12.6

12-33 Glial Cells and Brain Tumors

• Tumors—masses of rapidly dividing cells – Mature neurons have little or no capacity for mitosis and seldom form tumors

• Brain tumors arise from: – Meninges (protective membranes of CNS) – Metastasis from nonneuronal tumors in other organs – Often glial cells that are mitotically active throughout life

• Gliomas grow rapidly and are highly malignant – Blood–brain barrier decreases effectiveness of chemotherapy – Treatment consists of radiation or surgery

12-34 Myelin

• Myelin sheath—an insulating layer around a nerve fiber – Formed by oligodendrocytes in CNS and Schwann cells in PNS – Consists of the plasma membrane of glial cells • 20% protein and 80% lipid

• Myelination—production of the myelin sheath – Begins at week 14 of fetal development – Proceeds rapidly during infancy – Completed in late adolescence – Dietary fat is important to CNS development

12-35 Myelin

• In PNS, Schwann cell spirals repeatedly around a single nerve fiber – Lays down as many as a hundred layers of its own membrane – No cytoplasm between the membranes – Neurilemma: thick, outermost coil of myelin sheath • Contains nucleus and most of its cytoplasm • External to neurilemma is basal lamina and a thin layer of fibrous connective tissue—endoneurium

12-36 Myelin Sheath in PNS

Axolemma Neurilemma

Figure 12.4c

Nodes of Ranvier and internodes 12-37 Myelin

• In CNS—oligodendrocytes reach out to myelinate several nerve fibers in its immediate vicinity – Anchored to multiple nerve fibers – Cannot migrate around any one of them like Schwann cells – Must push newer layers of myelin under the older ones; so myelination spirals inward toward nerve fiber – Nerve fibers in CNS have no neurilemma or endoneurium

12-38 Myelin

• Many Schwann cells or oligodendrocytes are needed to cover one nerve fiber

• Myelin sheath is segmented

– Nodes of Ranvier: gap between segments – Internodes: myelin-covered segments from one gap to the next – Initial segment: short section of nerve fiber between the axon hillock and the first glial cell – Trigger zone: the axon hillock and the initial segment • Play an important role in initiating a nerve signal

12-39 Myelination in CNS

Oligodendrocyte

Myelin

Nerve fiber Figure 12.7b

(b) 12-40 Myelination in PNS

Axon Basal lamina Endoneurium

Nucleus

(a) Neurilemma Myelin sheath

Figure 12.7a

12-41 Diseases of the Myelin Sheath

• Degenerative disorders of the myelin sheath – Multiple sclerosis • Oligodendrocytes and myelin sheaths in the CNS deteriorate • Myelin replaced by hardened scar tissue • Nerve conduction disrupted (double vision, tremors, numbness, speech defects) • Onset between 20 and 40 and fatal from 25 to 30 years after diagnosis • Cause may be autoimmune triggered by virus

12-42 Diseases of the Myelin Sheath

• Degenerative disorders of the myelin sheath (cont.) – Tay–Sachs disease: a hereditary disorder of infants of Eastern European Jewish ancestry

• Abnormal accumulation of glycolipid called GM2 in the myelin sheath – Normally decomposed by lysosomal enzyme – Enzyme missing in individuals homozygous for Tay–Sachs allele

– Accumulation of ganglioside (GM2) disrupts conduction of nerve signals – Blindness, loss of coordination, and dementia • Fatal before age 4

12-43 Unmyelinated Nerve Fibers Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Neurilemma Myelin sheath

Unmyelinated nerve fibers

Myelinated axon

Schwann cell cytoplasm

Basal lamina

Neurilemma

Unmyelinated axon

Schwann cell (c) 3 µm Basal lamina c: © The McGraw-Hill Companies, Inc./Dr. Dennis Emery, Dept. of Zoology and Genetics, Iowa State University, photographer Figure 12.7c Figure 12.8

• Schwann cells hold 1 to 12 small nerve fibers in grooves on the surface • Membrane folds once around each fiber overlapping itself along the edges

• Mesaxon—neurilemma wrapping of unmyelinated nerve fibers 12-44 Conduction Speed of Nerve Fibers

• Speed at which a nerve signal travels along a nerve fiber depends on two factors – Diameter of fiber – Presence or absence of myelin • Signal conduction occurs along the surface of a fiber – Larger fibers have more surface area and conduct signals more rapidly – Myelin further speeds signal conduction

12-45 Conduction Speed of Nerve Fibers

• Conduction speed – Small, unmyelinated fibers: 0.5 to 2.0 m/s – Small, myelinated fibers: 3 to 15.0 m/s – Large, myelinated fibers: up to 120 m/s – Slow signals supply the stomach and dilate pupil where speed is less of an issue – Fast signals supply skeletal muscles and transport sensory – Signals for vision and balance

12-46 Regeneration of Nerve Fibers

• Regeneration of a damaged peripheral nerve fiber can occur if: – Its soma is intact – At least some neurilemma remains • Fiber distal to the injury cannot survive and degenerates – Macrophages clean up tissue debris at the point of injury and beyond • Soma swells, ER breaks up, and nucleus moves off center – Due to loss of nerve growth factor from neuron’s target cell • Axon stump sprouts multiple growth processes – Severed distal end continues to degenerate

12-47 Regeneration of Nerve Fibers

• Regeneration tube—formed by Schwann cells, basal lamina, and the neurilemma near the injury – Regeneration tube guides the growing sprout back to the original target cells and reestablishes synaptic contact

• Nucleus returns to normal shape

• Regeneration of damaged nerve fibers in the CNS cannot occur at all

12-48 Regeneration of Nerve Fiber

Neuromuscular junction Endoneurium Myelin sheath

Muscle fiber

1 Normal nerve fiber

Local trauma

Macrophages Degenerating terminal 2 Injured fiber • Denervation

Degenerating Schwann cells atrophy of muscle

Degenerating axon due to loss of nerve 3 Degeneration of severed fiber contact by damaged Schwann cells Growth processes

Regeneration nerve tube Atrophy of 4 Early regeneration muscle fibers

Retraction of growth processes

Growth processes 5 Late regeneration

Figure 12.9 Regrowth of muscle fibers 12-49 6 Regenerated fiber Nerve Growth Factor

• Nerve growth factor (NGF)— a protein secreted by a gland, muscle, and glial cells and picked up by the axon terminals of the neurons – Prevents apoptosis (programmed cell death) in growing neurons – Enables growing neurons to make contact with their target cells • Isolated by Rita Levi-Montalcini in 1950s • Won Nobel prize in 1986 with Stanley Cohen Figure 12.10 • Use of growth factors is now a vibrant field of research 12-50 Electrophysiology of Neurons

• Expected Learning Outcomes – Explain why a cell has an electrical charge difference (voltage) across its membrane. – Explain how stimulation of a neuron causes a local electrical response in its membrane. – Explain how local responses generate a nerve signal. – Explain how the nerve signal is conducted down an axon.

12-51 Electrophysiology of Neurons

• Galen thought that the brain pumped a vapor called psychic pneuma through hollow nerves and squirted it into the muscles to make them contract

• René Descartes in the seventeenth century supported this theory

• Luigi Galvani discovered the role of electricity in muscle contraction in the eighteenth century

• Camillo Golgi developed an important method for staining neurons with silver in the nineteenth century

12-52 Electrophysiology of Neurons

• Santiago Ramón y Cajal set forth the neuron doctrine: nervous pathway is not a continuous “wire” or tube, but a series of cells separated by gaps called synapses

• Neuron doctrine brought up two key questions – How does a neuron generate an electrical signal? – How does it transmit a meaningful message to the next cell?

12-53 Electrical Potentials and Currents

• Electrophysiology—cellular mechanisms for producing electrical potentials and currents – Basis for neural communication and muscle contraction

• Electrical potential—a difference in the concentration of charged particles between one point and another

• Electrical current—a flow of charged particles from one point to another – In the body, currents are movements of ions, such as Na+ or K+, through gated channels in the plasma membrane – Gated channels are opened or closed by various stimuli – Enables cell to turn electrical currents on and off

12-54 Electrical Potentials and Currents

• Living cells are polarized

• Resting membrane potential (RMP)—charge difference across the plasma membrane – About −70 mV in a resting, unstimulated neuron – Negative value means there are more negatively charged particles on the inside of the membrane than on the outside

12-55 The Resting Membrane Potential

• Resting membrane potential (RMP) exists because of unequal electrolyte distribution between extracellular fluid (ECF) and intracellular fluid (ICF) • RMP results from the combined effect of three factors – Ions diffuse down their concentration gradient through the membrane – Plasma membrane is selectively permeable and allows some ions to pass easier than others – Electrical attraction of cations and anions to each other

12-56 The Resting Membrane Potential

• Potassium ions (K+) have the greatest influence on RMP – Plasma membrane is more permeable to K+ than any other ion – Leaks out until electrical charge of cytoplasmic anions attracts it back in and equilibrium is reached and net diffusion of K+ stops – K+ is about 40 times as concentrated in the ICF as in the ECF • Cytoplasmic anions cannot escape due to size or charge (phosphates, sulfates, small organic acids, proteins, ATP, and RNA)

12-57 The Resting Membrane Potential

• Membrane much less permeable to high concentration of sodium (Na+) found outside the cell – Some leaks and diffuses into the cell down its concentration gradient – Na+ is about 12 times as concentrated in the ECF as in the ICF – Resting membrane is much less permeable to Na+ than to K+

12-58 The Resting Membrane Potential

• Na+/K+ pumps out 3 Na+ for every 2 K+ it brings in – Works continuously to compensate for Na+ and K+ leakage, and requires great deal of ATP • 70% of the energy requirement of the nervous system – Necessitates glucose and oxygen be supplied to nerve tissue (energy needed to create the resting potential) – Pump contributes about −3 mV to the cell’s resting membrane potential of −70 mV

12-59 The Resting Membrane Potential

ECF Figure 12.11 Na+ 145 m Eq/L K+ 4 m Eq/L

K+ Na+ channel channel Na+ 12 m Eq/L K+ 150 m Eq/L Large anions that cannot ICF escape cell • Na+ concentrated outside of cell (ECF) + • K concentrated inside cell (ICF) 12-60 Local Potentials

• Local potentials—disturbances in membrane potential when a neuron is stimulated

• Neuron response begins at the dendrite, spreads through the soma, travels down the axon, and ends at the synaptic knobs

12-61 Local Potentials

• When neuron is stimulated by chemicals, light, heat, or mechanical disturbance – Opens the Na+ gates and allows Na+ to rush into the cell – Na+ inflow neutralizes some of the internal negative charge – Voltage measured across the membrane drifts toward zero – Depolarization: case in which membrane voltage shifts to a less negative value – Na+ diffuses for short distance on the inside of the plasma membrane producing a current that travels toward the cell’s trigger zone; this short-range change in voltage is called a local potential 12-62 Local Potentials • Differences of local potentials from action potentials – Graded: vary in magnitude with stimulus strength • Stronger stimuli open more Na+ gates – Decremental: get weaker the farther they spread from the point of stimulation • Voltage shift caused by Na+ inflow diminishes rapidly with distance – Reversible: when stimulation ceases, K+ diffusion out of cell returns the cell to its normal resting potential – Either excitatory or inhibitory: some neurotransmitters (glycine) make the membrane potential more negative— hyperpolarize it—so it becomes less sensitive and less

likely to produce an action potential 12-63 Local Potentials

Current

ECF

Ligand Receptor

Plasma membrane of dendrite

Na+ ICF Figure 12.12 12-64 Action Potentials

• Action potential—more dramatic change produced by voltage-regulated ion gates in the plasma membrane – Only occur where there is a high enough density of voltage-regulated gates – Soma (50 to 75 gates per m2 ); cannot generate an action potential – Trigger zone (350 to 500 gates per m2 ); where action potential is generated • If excitatory local potential spreads all the way to the trigger zone and is still strong enough when it arrives, it can open these gates and generate an action potential 12-65 Action Potentials

• Action potential is a rapid up-and-down shift in the membrane voltage – Sodium ions arrive at the axon hillock – Depolarize the membrane at that point – Threshold: critical voltage to which local potentials must rise to open the voltage-regulated gates • −55 mV

• When threshold is reached, neuron “fires” and produces an action potential

• More and more Na+ channels open in the trigger zone in a positive feedback cycle creating a rapid rise in membrane voltage, called spike

12-66 Action Potentials • When rising membrane potential passes 0 mV, Na+ gates are inactivated – Begin closing; when all closed, the voltage peaks at +35 mV – Membrane now positive on the inside and negative on the outside – Polarity reversed from RMP—depolarization • By the time the voltage peaks, the slow K+ gates are fully open – K+ repelled by the positive intracellular fluid now exit the cell – Their outflow repolarizes the membrane; shifts the voltage back to negative numbers returning toward RMP 12-67 Action Potentials

– K+ gates stay open longer than the Na+ gates • Slightly more K+ leaves the cell than Na+ entering • Drops the membrane voltage 1 or 2 mV more negative than the original RMP—negative overshoot— hyperpolarization or afterpotential

– Na+ and K+ switch places across the membrane during an action potential

12-68 Action Potentials

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 4 • Only a thin layer of the +35 cytoplasm next to the cell membrane is 3 5 0 affected Depolarization Repolarization

Action

potential – In reality, very few ions mV Threshold 2 are involved –55 Local potential 1 7 • Action potential is often –70 Resting membrane 6 Hyperpolarization called a spike, as it potential

happens so fast (a) Time

Figure 12.13a 12-69 Action Potentials

• Characteristics of action Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. potential versus a local 4 +35 potential – Follows an all-or-none law 3 5 • If threshold is reached, 0 Depolarization Repolarization

neuron fires at its Action

potential maximum voltage mV Threshold 2 • If threshold is not reached, –55 it does not fire Local potential 1 – Nondecremental: do not 7 –70

get weaker with distance Resting membrane 6 Hyperpolarization potential – Irreversible: once started goes to completion and (a) Time cannot be stopped Figure 12.13a 12-70 Action Potential vs. Local Potential

Spike 3 5 0 0

Depolarization Repolarization

Action

potential mV mV Threshold 2 –55 Local potential 1 7 Hyperpolarization –70 Resting membrane 6 Hyperpolarization potential –70

Time 0 10 20 30 40 50 (a) (b) ms

Figure 12.13a,b

K+ Na+

K+ channel

Na+ channel

0 0

mV mV 1 Na+ and K+ channels closed 2 Na+ channels open, Na+ –70 enters cell, K+ channels –70 beginning to open Resting membrane Depolarization begins potential

35 35

0 0 Figure 12.14

mV mV 3 Na+ channels closed, K+ 4 Na+ channels closed, channels fully open, K+ –70 K+ channels closing –70 leaves cell Depolarization ends, Repolarization complete 12-72 repolarization begins The Refractory Period

Absolute Relative refractory refractory • During an action period period potential and for a few +35 milliseconds after, it is difficult or impossible to

stimulate that region of 0

a neuron to fire again mV

Threshold • Refractory period— –55 the period of resistance Resting membrane potential to stimulation –70

Time Figure 12.15

12-73 The Refractory Period

• Two phases of the refractory Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Absolute Relative period refractory refractory period period – Absolute refractory period +35 • No stimulus of any strength will trigger AP + • As long as Na gates are 0

open • From action potential to mV RMP Threshold – Relative refractory period –55 • Only especially strong Resting membrane potential stimulus will trigger new AP –70 – K+ gates are still open and any effect of Time incoming Na+ is opposed Figure 12.15 by the outgoing K+

12-74 The Refractory Period

Absolute Relative refractory refractory • The refractory period period period refers only to a small +35 patch of the neuron’s

membrane at one time 0

mV • Other parts of the neuron can be Threshold –55 stimulated while the Resting membrane potential small part is in –70 refractory period Time Figure 12.15

12-75 Signal Conduction in Nerve Fibers

• For communication to occur, the nerve signal must travel to the end of the axon

• Unmyelinated fiber has voltage-regulated ion gates along its entire length

• Action potential from the trigger zone causes Na+ to enter the axon and diffuse into adjacent regions beneath the membrane

12-76 Signal Conduction in Nerve Fibers

• The depolarization excites voltage-regulated gates immediately distal to the action potential • Na+ and K+ gates open and close producing a new action potential • By repetition the membrane distal to that is excited • Chain reaction continues to the end of the axon

Signal

Action potential + + + + – – – + + + + + + + + + + + – – – – + + + – – – – – – – – – – – in progress

Refractory membrane – – – – + + + – – – – – – – – – – – Excitable + + + + – – – + + + + + + + + + + + membrane

+ + + + + + + + + – – – + + + + + + – – – – – – – – – + + + – – – – – –

– – – – – – – – – + + + – – – – – – + + + + + + + + + – – – + + + + + +

+ + + + + + + + + + + + + – – – + + – – – – – – – – – – – – – + + + – – Figure 12.16

– – – – – – – – – – – – – + + + – – 12-78 + + + + + + + + + + + + + – – – + + Signal Conduction in Nerve Fibers

• Voltage-gated channels needed for APs – Fewer than 25 per m2 in myelin-covered regions (internodes) – Up to 12,000 per m2 in nodes of Ranvier • Fast Na+ diffusion occurs between nodes – Signal weakens under myelin sheath, but still strong enough to stimulate an action potential at next node • Saltatory conduction—nerve signal seems to jump from node to node Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Figure 12.17a

Na+ inflow at node Na+ diffuses along inside Excitation of voltage- generates action potential of axolemma to next node regulated gates will 12-79 (a) (slow but non decremental) (fast but decremental) generate next action potential here Signal Conduction in Nerve Fibers

+ + – – + + + + + + + + – – + + – – – – – – – – – – + + – – – – – – – – + + – – + + + + + + + +

+ + + + – – + + + + + + – – – – + + – – – – – – – – – – + + – – – – – – + + + + – – + + + + + +

+ + + + + + – – + + + + – – – – – – + + – – – – – – – – – – + + – – – – + + + + + + – – + + + +

Action potential Refractory Excitable (b) in progress membrane membrane

• Much faster than conduction in unmyelinated fibers

12-80 Synapses

• Expected Learning Outcomes – Explain how messages are transmitted from one neuron to another. – Give examples of neurotransmitters and neuromodulators and describe their actions. – Explain how stimulation of a postsynaptic cell is stopped.

12-81 Synapses

• A nerve signal can go no further when it reaches the end of the axon – Triggers the release of a neurotransmitter – Stimulates a new wave of electrical activity in the next cell across the synapse • Synapse between two neurons – First neuron in the signal path is the presynaptic neuron • Releases neurotransmitter – Second neuron is postsynaptic neuron • Responds to neurotransmitter

12-82 Synapses

• Presynaptic neuron may synapse with a dendrite, soma, or axon of postsynaptic neuron to form axodendritic, axosomatic, or axoaxonic synapses • A neuron can have an enormous number of synapses – Spinal motor neuron covered by about 10,000 synaptic knobs from other neurons • 8,000 ending on its dendrites • 2,000 ending on its soma • In the cerebellum of brain, one neuron can have as many as 100,000 synapses

12-83 The Discovery of Neurotransmitters

Presynaptic Directionof Postsynaptic neuron signal neuron transmission

(a)

Axodendritic synapse Figure 12.18

Axosomatic synapse

Axoaxonic synapse

(b) 12-84 The Discovery of Neurotransmitters

• Synaptic cleft—gap between neurons was discovered by Ramón y Cajal through histological observations • Otto Loewi, in 1921, demonstrated that neurons communicate by releasing chemicals—chemical synapses – He flooded exposed hearts of two frogs with saline – Stimulated vagus nerve of the first frog and the heart slowed – Removed saline from that frog and found it slowed heart of second frog – Named it Vagusstoffe (“vagus substance”) • Later renamed acetylcholine, the first known neurotransmitter

12-85 The Discovery of Neurotransmitters

• Electrical synapses do exist – Some neurons, neuroglia, and cardiac and single-unit smooth muscle – Gap junctions join adjacent cells • Ions diffuse through the gap junctions from one cell to the next – Advantage of quick transmission • No delay for release and binding of neurotransmitter • Cardiac and smooth muscle and some neurons – Disadvantage is they cannot integrate information and make decisions • Ability reserved for chemical synapses in which neurons communicate by releasing neurotransmitters

12-86 Synaptic Knobs

Axon of presynaptic neuron Synaptic knob

Soma of postsynaptic neuron

Figure 12.19 12-87 Structure of a Chemical Synapse

• Synaptic knob of presynaptic neuron contains synaptic vesicles containing neurotransmitter – Many docked on release sites on plasma membrane • Ready to release neurotransmitter on demand – A reserve pool of synaptic vesicles located further away from membrane

• Postsynaptic neuron membrane contains proteins that function as receptors and ligand- regulated ion gates

12-88 Structure of a Chemical Synapse

Microtubules ofcytoskeleton

Axon of presynaptic neuron Mitochondria

Postsynaptic neuron Synaptic knob

Synaptic vesicles containing neurotransmitter Synaptic cleft

Neurotransmitter receptor Neurotransmitter Postsynaptic neuron release

• Presynaptic neurons have synaptic vesicles with neurotransmitter and postsynaptic have receptors and ligand-regulated ion channels 12-89 Neurotransmitters and Related Messengers • More than 100 neurotransmitters have been identified • Fall into four major categories according to chemical composition – Acetylcholine • In a class by itself • Formed from acetic acid and choline – Amino acid neurotransmitters • Include glycine, glutamate, aspartate, and -aminobutyric acid (GABA)

12-90 Neurotransmitters and Related Messengers Cont. – Monoamines • Synthesized from amino acids by removal of the –COOH group

• Retaining the –NH2 (amino) group • Major monoamines – Epinephrine, norepinephrine, dopamine (catecholamines) – Histamine and serotonin

– Neuropeptides

12-91 Neurotransmitters and Related Messengers

Acetylcholine Monoamines Neuropeptides Met CH O Phe 3 Catecholamines Gly Gly + Gly Met H C N C H CH O C C H OH Try Leu 3 2 2 3 Phe Gly HO CH CH NH CH Phe CH 3 2 2 Enkephalin Glu Glu Substance P HO Epinephrine Pro Ary Try Lys Amino acids OH O HO CH2 CH2 NH2 C CH CH CH NH 2 2 2 HO Norepinephrine Phe HO Met Asp GABA Asp Tyr Met Gly Trp Met O HO CH2 CH2 NH2 Thr Met C CH NH Ser Phe HO HO Dopamine Gly SO4 Cholecystokinin Glycine Glu Gly Try O O Lys C CH CH C HO CH CH NH HO 2 2 2 NH OH Ser ß-endorphin 2 N Asparticacid Serotonin N Glu O O Lys Asn Ala C CH CH CH C CH2 CH2 NH2 Lys Tyr HO 2 2 O H N Ile NH Histamine Thr Ile Lys 2 Glutamic acid Ala Pro Asn Lys Lys Leu Phe Gly Val Leu Thr Glu

Figure 12.21

12-92 Neurotransmitters and Related Messengers

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • Neuropeptides are chains of 2 to Neuropeptides Met Phe Gly Gly 40 amino acids Try Leu Met Phe Gly Phe Enkephalin Glu – Beta-endorphin and substance P Glu Substance P Pro • Act at lower concentrations than Ary Try Lys

other neurotransmitters Phe Met Asp Asp Tyr Met Gly Trp Met • Longer lasting effects Thr Met Ser Phe Gly SO4 Cholecystokinin • Stored in axon terminal as larger Glu Gly Try secretory granules (called dense- Lys core vesicles) Ser ß-endorphin

Glu Asn • Some function as hormones or Lys Asn Ala Ile Tyr Thr Ile Lys neuromodulators Ala Pro Asn Lys • Some also released from digestive Lys Leu Phe Gly Val Leu tract Thr Glu – Gut–brain peptides cause food cravings Figure 12.21

12-93 Synaptic Transmission

• Neurotransmitters – Synthesized by the presynaptic neuron – Released in response to stimulation – Bind to specific receptors on the postsynaptic cell – Alter the physiology of that cell

12-94 Synaptic Transmission

• A given neurotransmitter does not have the same effect everywhere in the body

• Multiple receptor types exist for a particular neurotransmitter – 14 receptor types for serotonin

• Receptor governs the effect the neurotransmitter has on the target cell

12-95 Synaptic Transmission

• Neurotransmitters are diverse in their action – Some excitatory – Some inhibitory – Some the effect depends on what kind of receptor the postsynaptic cell has – Some open ligand-regulated ion gates – Some act through second-messenger systems

12-96 Synaptic Transmission

• Three kinds of synapses with different modes of action – Excitatory cholinergic synapse – Inhibitory GABA-ergic synapse – Excitatory adrenergic synapse

• Synaptic delay—time from the arrival of a signal at the axon terminal of a presynaptic cell to the beginning of an action potential in the postsynaptic cell – 0.5 ms for all the complex sequence of events to occur

12-97 An Excitatory Cholinergic Synapse

• Cholinergic synapse—employs acetylcholine (ACh) as its neurotransmitter – ACh excites some postsynaptic cells • Skeletal muscle – Inhibits others

12-98 An Excitatory Cholinergic Synapse

Presynaptic neuron

Figure 12.22

Presynaptic neuron 3 Ca2+

2 ACh

Na+

5 K+

Postsynaptic neuron 12-99 An Inhibitory GABA-ergic Synapse

• GABA-ergic synapse employs -aminobutyric acid as its neurotransmitter

• Nerve signal triggers release of GABA into synaptic cleft

• GABA receptors are chloride channels

• Cl− enters cell and makes the inside more negative than the resting membrane potential

• Postsynaptic neuron is inhibited, and less likely to fire

12-100 An Excitatory Adrenergic Synapse

• Adrenergic synapse employs the neurotransmitter norepinephrine (NE), also called noradrenaline • NE and other monoamines, and neuropeptides, act through second-messenger systems such as cyclic AMP (cAMP) • Receptor is not an ion gate, but a transmembrane protein associated with a G protein • Slower to respond than cholinergic and GABA-ergic synapses • Has advantage of enzyme amplification—single molecule of NE can produce vast numbers of product molecules in the cell 12-101 An Excitatory Adrenergic Synapse

Presynaptic neuron

Postsynaptic neuron

Neurotransmitter receptor Norepinephrine Adenylate cyclase G protein – – – + + + 1 Ligand- 2 3 gated 5 Na+ channels opened cAMP

4 Postsynaptic potential Multiple Enzyme activation possible 6 effects 7 Figure 12.23 Metabolic changes Genetic transcription

Enzyme synthesis 12-102 Cessation of the Signal

• Mechanisms to turn off stimulation to keep postsynaptic neuron from firing indefinitely – Neurotransmitter molecule binds to its receptor for only 1 ms or so • Then dissociates from it – If presynaptic cell continues to release neurotransmitter • One molecule is quickly replaced by another and the neuron is restimulated

12-103 Cessation of the Signal

• Stop adding neurotransmitter and get rid of that which is already diffusion – Neurotransmitter escapes the synapse into the nearby ECF – Astrocytes in CNS absorb it and return it to neurons • Reuptake – Synaptic knob reabsorbs amino acids and monoamines by endocytosis – Break neurotransmitters down with monoamine oxidase (MAO) enzyme – Some antidepressant drugs work by inhibiting MAO • Degradation in the synaptic cleft – Enzyme acetylcholinesterase (AChE) in synaptic cleft degrades ACh into acetate and choline – Choline reabsorbed by synaptic knob 12-104 Neuromodulators

• Neuromodulators—hormones, neuropeptides, and other messengers that modify synaptic transmission – May stimulate a neuron to install more receptors in the postsynaptic membrane adjusting its sensitivity to the neurotransmitter – May alter the rate of neurotransmitter synthesis, release, reuptake, or breakdown

• Enkephalins—a neuromodulator family – Small peptides that inhibit spinal interneurons from transmitting pain signals to the brain

12-105 Neuromodulators

• Nitric oxide (NO)—simpler neuromodulator – A lightweight gas released by the postsynaptic neurons in some areas of the brain concerned with learning and memory – Diffuses into the presynaptic neuron – Stimulates it to release more neurotransmitter – One neuron’s way of telling the other to “give me more” – Some chemical communication that goes backward across the synapse

12-106 Neural Integration

• Expected Learning Outcomes – Explain how a neurons “decides” whether or not to generate action potentials. – Explain how the nervous system translates complex information into a simple code. – Explain how neurons work together in groups to process information and produce effective output. – Describe how memory works at cellular and molecular levels.

12-107 Neural Integration

• Synaptic delay slows the transmission of nerve signals

• More synapses in a neural pathway, the longer it takes for information to get from its origin to its destination – Synapses are not due to limitation of nerve fiber length – Gap junctions allow some cells to communicate more rapidly than chemical synapses

12-108 Neural Integration

• Then why do we have synapses? – To process information, store it, and make decisions – Chemical synapses are the decision-making devices of the nervous system – The more synapses a neuron has, the greater its information-processing capabilities – Pyramidal cells in cerebral cortex have about 40,000 synaptic contacts with other neurons – Cerebral cortex (main information-processing tissue of your brain) has an estimated 100 trillion (1014) synapses

• Neural integration—the ability of your neurons to process information, store and recall it, and make decisions 12-109 Postsynaptic Potentials

• Neural integration is based on the postsynaptic potentials produced by neurotransmitters

• Typical neuron has a resting membrane potential of −70 mV and threshold of about −55 mV

12-110 Postsynaptic Potentials

• Excitatory postsynaptic potential (EPSP) – Any voltage change in the direction of threshold that makes a neuron more likely to fire • Usually results from Na+ flowing into the cell cancelling some of the negative charge on the inside of the membrane

– Glutamate and aspartate are excitatory brain neurotransmitters that produce EPSPs

12-111 Postsynaptic Potentials

• Inhibitory postsynaptic potential (IPSP) – Any voltage change away from threshold that makes a neuron less likely to fire • Neurotransmitter hyperpolarizes the postsynaptic cell and makes it more negative than the RMP making it less likely to fire • Produced by neurotransmitters that open ligand-regulated chloride gates – Causing inflow of Cl− making the cytosol more negative

12-112 Postsynaptic Potentials

Cont.

– Glycine and GABA produce IPSPs and are inhibitory

– Acetylcholine (ACh) and norepinephrine are excitatory to some cells and inhibitory to others • Depending on the type of receptors on the target cell • ACh excites skeletal muscle, but inhibits cardiac muscle due to the different type of receptors

12-113 Postsynaptic Potentials

–20

–40 mV Threshold

–60 EPSP Resting membrane potential

Repolarization –80 Depolarization

(a) Stimulus Time 0

–20

–40 mV Threshold

–60 Resting membrane potential IPSP

–80 Hyperpolarization Figure 12.24

Stimulus Time (b) 12-114 Summation, Facilitation, and Inhibition

• One neuron can receive input from thousands of other neurons • Some incoming nerve fibers may produce EPSPs while others produce IPSPs • Neuron’s response depends on whether the net input is excitatory or inhibitory • Summation—the process of adding up postsynaptic potentials and responding to their net effect – Occurs in the trigger zone

12-115 Summation, Facilitation, and Inhibition

• The balance between EPSPs and IPSPs enables the nervous system to make decisions • Temporal summation—occurs when a single synapse generates EPSPs so quickly that each is generated before the previous one fades – Allows EPSPs to add up over time to a threshold voltage that triggers an action potential • Spatial summation—occurs when EPSPs from several different synapses add up to threshold at an axon hillock – Several synapses admit enough Na+ to reach threshold – Presynaptic neurons cooperate to induce the postsynaptic neuron to fire

12-116 Temporal and Spatial Summation

3 Postsynaptic neuron fires 2 EPSPs spread from one synapse to trigger zone 1 Intense stimulation by one presynaptic neuron

(a) Temporal summation

3 Postsynaptic neuron fires 2 EPSPs spread from several synapses to trigger zone 1 Simultaneous stimulation by several presynaptic neurons

(b) Spatial summation Figure 12.25 12-117 Summation of EPSPs

+40

+20

Action potential

mV –20

–40 Threshold

–60 EPSPs

Resting –80 Stimuli membrane potential Figure 12.26 Time • Does this represent spatial or temporal summation? 12-118 Summation, Facilitation, and Inhibition • Neurons routinely work in groups to modify each other’s action • Facilitation—a process in which one neuron enhances the effect of another one – Combined effort of several neurons facilitates firing of postsynaptic neuron

Signal in inhibitory neuron Figure 12.27

No activity in inhibitory neuron

No neurotransmitter Neurotransmitter release here Inhibition of presynaptic IPSP neuron S S Neurotransmitter No neurotransmitter release here Excitation of postsynaptic + R No response in postsynaptic R neuron EPSP neuron (a) (b) 12-119 Summation, Facilitation, and Inhibition • Presynaptic inhibition—process in which one presynaptic neuron suppresses another one – Opposite of facilitation – Reduces or halts unwanted synaptic transmission – Neuron I releases inhibitory GABA • Prevents voltage-gated calcium channels from opening in synaptic knob and presynaptic neuron releases less or no neurotransmitter

Figure 12.27 Signal in inhibitory neuron

No activity in inhibitory neuron

• Neural coding—the way in which the nervous system converts information to a meaningful pattern of action potentials

• Qualitative information depends upon which neurons fire – Labeled line code: each nerve fiber to the brain leads from a receptor that specifically recognizes a particular stimulus type

12-121 Neural Coding

• Quantitative information—information about the intensity of a stimulus is encoded in two ways – One depends on the fact that different neurons have different thresholds of excitation • Stronger stimuli causes a more rapid firing rate • Excitement of sensitive, low-threshold fibers gives way to excitement of less sensitive, high-threshold fibers as intensity of stimuli increases

12-122 Neural Coding

Cont. – Other way depends on the fact that the more strongly a neuron is stimulated, the more frequently it fires • CNS can judge stimulus strength from the firing frequency of afferent neurons

12-123 Neural Coding

2 g

5 g

10 g

20 g

Time Figure 12.28 12-124 Neural Pools and Circuits

• Neural pools—neurons function in large groups, each of which consists of millions of interneurons concerned with a particular body function – Control rhythm of breathing – Moving limbs rhythmically when walking Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Input neuron

Figure 12.29

Facilitated zone Discharge zone Facilitated zone 12-125 Neural Pools and Circuits

• Information arrives at a neural pool through one or more input neurons – Branch repeatedly and synapse with numerous interneurons in the pool – Some input neurons form multiple synapses with a single postsynaptic cell • Can produce EPSPs in all points of contact with that cell • Through spatial summation, make it fire more easily than if they synapsed with it at only one point

12-126 Neural Pools and Circuits

Cont. – Within the discharge zone of an input neuron • That neuron acting alone can make the postsynaptic cells fire – In a broader facilitated zone, it synapses with still other neurons in the pool • Fewer synapses on each of them • Can only stimulate those neurons to fire with the assistance of other input neurons

12-127 Neural Pools and Circuits

• Diverging circuit – One nerve fiber branches and synapses with several postsynaptic cells – One neuron may produce output through hundreds of neurons

• Converging circuit – Input from many different nerve fibers can be funneled to one neuron or neural pool – Opposite of diverging circuit

12-128 Neural Pools and Circuits

Cont. • Reverberating circuits – Neurons stimulate each other in linear sequence but one cell restimulates the first cell to start the process all over – Diaphragm and intercostal muscles

• Parallel after-discharge circuits – Input neuron diverges to stimulate several chains of neurons • Each chain has a different number of synapses • Eventually they all reconverge on a single output neuron • After-discharge—continued firing after the stimulus stops

12-129 Neural Pools and Circuits

Diverging Converging

Input Output

Output Input

Reverberating Parallel after-discharge

Figure 12.30

Input Output Input Output 12-130 Memory and Synaptic Plasticity

• Physical basis of memory is a pathway through the brain called a memory trace or engram – Along this pathway, new synapses were created or existing synapses modified to make transmission easier – Synaptic plasticity: the ability of synapses to change – Synaptic potentiation: the process of making transmission easier

• Kinds of memory – Immediate, short- and long-term memory – Correlate with different modes of synaptic potentiation

12-131 Immediate Memory

• Immediate memory—the ability to hold something in your thoughts for just a few seconds – Essential for reading ability • Feel for the flow of events (sense of the present) • Our memory of what just happened “echoes” in our minds for a few seconds – Reverberating circuits

12-132 Short-Term Memory • Short-term memory (STM)—lasts from a few seconds to several hours – Quickly forgotten if distracted – Calling a phone number we just looked up – Reverberating circuits

• Facilitation causes memory to last longer – Tetanic stimulation: rapid arrival of repetitive signals at a synapse • Causes Ca2+ accumulation and postsynaptic cell more likely to fire – Posttetanic potentiation: to jog a memory • Ca2+ level in synaptic knob stays elevated

• Little stimulation needed to recover memory 12-133 Long-Term Memory

• Types of long-term memory – Declarative: retention of events that you can put into words – Procedural: retention of motor skills

• Physical remodeling of synapses – New branching of axons or dendrites

• Molecular changes—long-term potentiation – Changes in receptors and other features increase transmission across “experienced” synapses – Effect is longer-lasting

12-134 Long-Term Memory

• Molecular changes are called long-term potentiation

• Method described – Receptors on synaptic knobs are usually blocked by Mg2+ ions – When they bind glutamate and receive tetanic stimuli, they repel Mg2+ and admit Ca2+ into the dendrite; Ca2+ acts as second messenger • More synaptic knob receptors are produced • Synthesizes proteins involved in synapse remodeling • Releases nitric oxide that triggers more neurotransmitter release at presynaptic neuron 12-135 Alzheimer Disease

• 100,000 deaths/year – 11% of population over 65; 47% by age 85

• Memory loss for recent events, moody, combative, lose ability to talk, walk, and eat

• Show deficiencies of acetylcholine (ACh) and nerve growth factor (NGF)

• Diagnosis confirmed at autopsy – Atrophy of gyri (folds) in cerebral cortex – Neurofibrillary tangles and senile plaques – Formation of β-amyloid protein from breakdown product of plasma membranes

• Treatment—halt β-amyloid production – Research halted due to serious side effects

– Give NGF or cholinesterase inhibitors 12-136 Alzheimer Disease

Neurons with neurofibrillary tangles Shrunken gyri

Wide sulci Senile plaque

(a) a: Custom Medical Stock Photo

Figure 12.31a Figure 12.31b

12-137 Parkinson Disease

• Progressive loss of motor function beginning in 50s or 60s— no recovery – Degeneration of dopamine-releasing neurons • Dopamine normally prevents excessive activity in motor centers (basal nuclei) • Involuntary muscle contractions – Pill-rolling motion, facial rigidity, slurred speech – Illegible handwriting, slow gait • Treatment—drugs and physical therapy – Dopamine precursor (L-dopa) crosses brain barrier; bad side effects on heart and liver – MAO inhibitor slows neural degeneration – Surgical technique to relieve tremors

12-138