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    Lecture: Neurophysiology

    I. Overview of Nervous System Organization

    A. Central Nervous System (CNS) - brain and spinal cord

    B. Peripheral Nervous System (PNS) spinal/cranial nerves

    1. Sensory (Afferent) Division - TO the CNS

    a. somatic afferents - from skin, muscle, jointsb. visceral afferents - from membranes & organs

    2. Motor (Efferent) Division - FROM the CNS

    a. Somatic Nervous System (Voluntary) - to skeletal musclesb. Autonomic Nervous System (Involuntary) - to organs & glands

    i. Sympathetic Division

    ii. Parasympathetic Division

    II. The Structure of a Neuron (Nerve Cell)

    A. neuron - special cells of nervous system that carry messages in the form of electrical

    Impulses

    B. Supporting Cells of Neurons

    1. Support Cells of the CNS (Glial Cells)

    a. astrocytes - regulate environmentaround neurons and selective transport

    from capillariesb. microglia -eat infectious microbes of CNSc. ependymal cells - line cavities of brain

    and spinal cord, flushing cerebrospinal

    fluid (CFS)d. oligodendrocytes - form myelin sheaths

    around axons of CNS; increase speed of

    impulses

    2. Support Cells of the PNS

    a. Schwann cells form "myelin sheaths" around axons; also assist inregeneration of axon

    b. satellite cells - control chemical environment

    C. Special Characteristics of Neurons

    1. amitotic - "not mitotic"; they cannot reproduce or regenerate after certain

    point in life

    2. longevity - neurons can survive entire lifetime

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    3. high metabolic rate - require OXYGEN and GLUCOSE at all times

    D. Neuron Cell Body (soma; perikaryon)

    1. major part from which the processes (axons and dendrites) project; 5-140

    micron diameter2. single large spherical nucleus with nucleolus

    3. Nissl Bodies - Rough Endoplasmic Reticulum (rER); make proteins and

    plasma membrane4. nucleus - a collection of cell bodies in the CNS

    5. ganglion - a collection of cell bodies in the PNS

    E. Typical Neuron Processes (Dendrites & Axon)

    1. dendrites - branching, rootlike extensions off the cell body

    receptive/input component of the neuron; incoming signals are forwarded to the cell bodysignals of dendrites are NOT all-or-none action potentials, but are graded potentials that

    result from summation of inputs

    2. axon - extension that carries an all-or-nothing action potential from the

    cell body to the target; conducting component of the neuron connecting it

    to other cells or neurons

    a. tract - a bundle of axons in the CNS

    b. nerve - a bundle of axons in the PNSc. axolemma - plasma membrane of neuron

    d. axon hillock - the cone-shaped region of attachment of the axon to the

    cell body; site where action potential is triggerede. axon collaterals- rare branches of an axon

    f. telodendria - typical terminal branches of an axon which may number

    up to 15,000g. synaptic knobs/ boutons/ axon terminals - at the end of each

    telodendria, abut the target tissue to secrete a chemical

    neurotransmitter; secretory component of the neuron

    h. axon depends upon the cell body for everything: organelles, proteins,and enzymes for synthesis of neurotransmitter

    i. anterograde transport - movement of material from cell body to

    synaptic knobsii. retrograde transport - movement of material from synapse to

    cell body

    3. myelin sheath - wrap of Scwhann cells (PNS) and oligodendricytes (CNS)

    around the axon

    a. increases speed of action potential signal [myelinated (150 m/s);

    unmyelinated (1 m/s)]b. nodes of Ranvier - gaps between myelin cells at regular intervals on axon

    c. white matter of brain - areas with myelinated axons

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    d. gray matter of brain - areas with cell bodies and unmyelinated cell

    processes

    F. Structural Classification of Neurons

    1. multipolar neuron - has three or more cell processes; typically many dendrites andone axon (throughout the CNS)

    2. bipolar neuron - have two (bi) processes: one dendrite and one axon, eachextending from opposite sides of the cell body (retina of the eye)

    3. unipolar neuron - one long process attached to the cell body by a T like

    extensiona. peripheral process the part that starts at the sensory receptor (eg. Skin)

    b. central process the part that terminates in the CNS (eg. Spinal cord)

    G. Functional Classification of Neurons

    1. sensory (afferent) neuron - transmit impulses from sensory receptors TOWARDthe CNS

    a. almost all are unipolar and located just outside the spinal column

    i. Dorsal Root Ganglion of the spinal cord (sensory info from body)

    2. motor (efferent) neuron - transmit impulses AWAY FROM the CNS to the target

    tissue

    a. almost all are multipolar, with cell bodies in the CNS

    3. association neuron (interneuron) between sensory and motor neurons

    III. Basic Principles of Electricity

    A. voltage (potential difference/potential) - measure of the potential energy that results

    from the separation of Positive and Negative charges

    1. more charge separated = larger voltageless charge separated = smaller voltage

    2. volts - units of voltagemillilvolt (mV) = l/l000 volt (typical unit used for membrane voltages)

    B. current - the flow of electrical charges from one area to another (eg. Na+ into a cell)

    1. currents in the body are usually the flow of ions (Na+, K+, Cl-, Ca++)

    2. voltage - greater the separation of charge, themore "potential energy" for current to move

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    3. resistance - the hindrance to the flow of charge through which current must pass

    (plasma membrane and ion channels)

    a. insulator - HIGH resistance (low current)

    (eg. rubber, wire insulation material)

    b. conductor - LOW resistance (high current)(eg. copper wire, water, most metals)

    C. Ohm's Law voltage (V), current (I), resistance (R)

    current (I) = voltage (V)

    resistance (R)

    INCREASED voltage = INCREASED current

    DECREASED voltage = DECREASED current

    INCREASED resistance = DECREASED currentDECREASED resistance = INCREASED current

    D. Regulation of Current/Voltage - Changing Resistance (Permeability) of Cell

    Membrane

    1. leakage channels - channels that are always open (eg. K+ leakage channels)

    2. chemical-gated (ligand-gated) channels open

    or close when bound by a specific molecule

    (eg. neurotransmitter: ACh, serotonin, etc.)

    3. voltage-gated (dependent) channels - open or

    close depending on the voltage acrossmembrane

    E. electrochemical gradient - net result of both the "electrical gradient" and "chemicalgradient"

    1. electrical gradient - positive charges move

    toward negative charges and vice versa2. chemical gradient - diffusion from area of

    high concentration to low concentration

    IV. Resting Membrane Potential of a Neuron: A Polarized State

    A. Review of Polarized State

    1. Na+-K+= ATPase Pump

    [Na+]out > [Na+]in

    [K+]out < [K+]inK+ leaks out of the cell

    2. K+ Leak Channels

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    3. Na+ channels are closed at rest

    4. Cl levels [Cl-]out > [Cl-]in

    Chloride ions can also leak into the cell, but the electrical gradient (due to

    negative charge inside of the cell) balances the chemical gradient for Cl- to rush

    in.

    V. Membrane Potential and Signaling

    A. Definition of Terms - (relative to resting membrane potential -70 mV)

    1. depolarization - inside of cell becomes less negative; the resting potential

    approaches ZERO or becomes positive (e.g. Na+ moves into the cell)

    -70 mV-50 mV-30 mV0 mV+20 mV +60 mV

    2. hyperpolarization - inside of the cell becomes even more negative; the restingmembrane potential gets larger (more K+ and/or Cl- channels open; K+ moves

    out, and Cl- moves in)

    -120 mV -100 mV -80 mV -70 mV

    B. graded potentials - short-term, localized depolarization or hyperpolarization that

    depends on the intensity of the stimulus; the larger the stimulus, the greater the

    change in voltage and the farther the current spreads in cell

    Graded potentials are localized - their intensity gradually dies out at further distancesfrom the point of stimulation - like ripples in a pond when a rock is dropped.decremental - it decreases over distance.

    1. postsynaptic potential - potential generated by neurotransmitter on thepostsynaptic cell

    2. receptor potential - potential generated by a stimulus (heat, light, stretch) in a

    sensory neuron

    C. action potential - an all-or-none, uni-directional wave of depolarization along the

    length of a cell (such as the axon of a neuron; called a nerve impulse)

    Steps in Action Potential generation:

    1. depolarization due to opening of Na+ channels

    When the membrane at the axon hillock is depolarized to a threshold level (-50 mV),

    voltage-gated Na+ channels are triggered to open, allowing Na+ to rush in, causingfurther depolarization, and even more Na+ channels to open. This positive feedback

    loop is called Hodgkin Cycle, after the discoverer. This phenomenon spreads down

    the axon like a series of falling dominos, in an "all-or-none" fashion.

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    2. immediate closure of the voltage-gated Na+ channels

    Only 3 ms after a voltage-dependent Na+ channel opens, it closes, so that Na+ can no

    longer enter the cell, and the resting potential can be regenerated. However, the local

    depolarizing effect of the opening has already been passed on, causing the actionpotential.

    3. repolarization due to opening of K+ channels

    As the Na+ channels close, voltage-dependent K+ channels open, allowing even more

    K+ to rush out of the cell, until the resting membrane potential is restored.

    D. threshold - the level of depolarization that will trigger an action potential (the level at

    which voltage-dependent Na+ channels are triggered to open)

    E. Stimulus Intensity - Coded by Action Potential Frequency

    The strength of a stimulus is translated by the neuron by the FREQUENCY (# persecond) of action potentials. The more pressure on the skin, the faster are the impulses in

    afferent axon.

    F. Absolute Refractory Period - while Na+ channels are open, it is impossible togenerate another action potential

    G. Relative Refractory Period - when Na+ channels are closed, and K+ channelsregenerate the resting potential, action potentials can occur, but the stimulus must be

    greater than before

    H. Factors that Influence Speed of Action Potential

    1. axon diameter - larger diameter = faster impulse2. myelin sheath - increases the speed of impulse domino effect jumps between the

    nodes of Ranvier (called saltatory conduction)

    a. multiple sclerosis - loss of myelin

    I. Classification of Nerve Fibers

    1. Group A fibers - large diameter/thick myelin (sensory and motor fibers of skin,muscle, joints)

    2. Group B fibers - medium diameter/light myelin

    3. Group C fibers - small diameter/ no myelin

    VI. The Synapse: Axon Terminal Meets Postsynaptic Cell

    A. synapse - the junction of a neuron that allows transfer of message to "postsynaptic

    cell" (eg. another neuron, muscle fiber, gland, etc.)

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    1. axodendritic - axon terminal -> dendrite

    2. axosomatic - axon terminal -> neuron cell body3. axonaxonic - axon terminal -> another axon

    4. dendrodendritic - dendrite -> dendrite

    5. dendrosomatic - dendrite -> neuron cell body6. neuromuscular junction - axon terminal -> muscle

    7. neuroglandular junction - axon terminal ->gland

    8. presynaptic neuron - "before" the synapse; the neuron that is sending the signal9. postsynaptic neuron - "after" the synapse; the affected cell receiving the signal

    B. Electrical Synapse - "electrically coupled" cells that have "bridged junctions",allowing the direct passage of ions from one cell into the next.

    1. allows for direct synchronization of activity

    C. Chemical Synapse - a synapse which relies on the passage of a "neurotransmitter" (eg.

    ACh) across the synaptic cleft, which binds to chemically-gated ion channels on thepostsynaptic cell.

    VII. Transmission of Signal Across a Chemical Synapse

    1. Depolarization of Presynaptic Axon Terminal - when an action potential reaches

    the axon terminal, the influx of Na+ ions causes it to become depolarized

    2. Depolarization Opens Voltage-Gated Ca++ Channels - In response the

    depolarization of the axon terminal, voltage-dependent Ca++ channels on

    presynaptic axon terminal open, allowing Ca++ to rush INTO the cell down itsconcentration gradient

    3. Increased Ca++ Causes Neurotransmitter Release - As Ca++ increases in the axonterminal, synaptic vesicles containing the neurotransmitter fuse with the plasma

    membrane, releasing contents into the synaptic cleft

    4. Neurotransmitter Binds Receptor - Opens Ion Channels - The releasedneurotransmitter crosses the synaptic cleft reversibly binds to receptors, opening

    either EXCITATORY ion channels (Na+ moves in to depolarize) or

    INHIBITORY ion channels (Cl-/K+ move to hyperpolarize)

    Excitatory, Postsynpatic Potentials (EPSPs) - Depolarization - Leads to MORE ActionPotentials

    EPSPs result when a neurotransmitter opens Na+ channels, causing depolarization of the

    cell body, and increased likelihood of generating an axon potential. EPSPs are gradedpotentials, meaning they are localized and dissipate over a distance. For an action

    potential to be generated on the postsynaptic cell, the "threshold" voltage must be

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    obtained at the axon hillock. This occurs through temporal summation and/or spatial

    summation of many EPSPs from up to10,000 incoming axons terminals on the

    postsynaptic cell body.

    Inhibitory Postsynaptic Potentials (IPSPs) - Hyperpolarization - Leads to LESS Action

    Potentials

    IPSPs result when a neurotransmitter opens either Cl- channels, K+ channels, or both,

    causing hyperpolarization of the cell body (-l00 mv), and decreased likelihood ofgenerating an action potential. Like EPSPs, IPSPs are graded potentials that are

    localized and dissipate over a distance. The "integration" of EPSPs and IPSPs through

    both temporal summation and spatial summation is how the postsynaptic cell makes

    the "decision" whether or not to fire an action potential. If, after all EXCITATORYand INHIBITORY input, the axon hillock reaches the "threshold" voltage, the

    postsynaptic cell will fire an action potential.

    5. Termination of Neurotransmitter Effects

    The EPSPs and IPSPs are terminated when the neurotransmitter is released from the

    receptor 3 ms), ending the flow of ions. The neurotransmitter may be degraded by

    enzymes (eg. acetylcholinesterase), may be reabsorbed by the presynaptic cell (eg.

    norepinephrine), or may diffuse away from the synapse.

    VIII. Structure and Function Classifications of Neurotransmitters

    A. General Characteristics of Neurotransmitters

    1. Most neurons release only one neurotransmitter, but some may release two ormore

    2. more than 100 neurotransmitters are known

    3. Neurotransmitters may be synthesized in the axon terminal, or in the cell bodyand then transported. In either case, the synthesizing enzymes are made in the cell

    body.

    B. Classification by Chemical Structure

    1. Acetylcholine (ACh)

    a. skeletal muscle, some autonomic neurons, and various parts of the CNS

    b. choline acetyltransferase - synthesis enzyme

    c. acetylcholinesterase - breakdown enzymed. breakdown product (choline) is recaptured by presynaptic axon for resynthesis

    of ACh

    e. reuptake inhibitors - drugs that block the reuptake (Prozac - serotonin for

    depression)f. nerve gas, malathion - block the activity of aceytlcholinesterase

    g. some snake/spider venoms - block ACh receptor

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    2. Biogenic Amines

    catecholamines - dopamine, norepinephrine (NE), and epinephrine

    a. common biosynthetic pathwayb. enzymes determine final product in neuron

    c. tyrosine is precursor to all of these

    d. Dopamine blockers - used to treat Schizophrenia (thorazine &haloperidol)

    e. Amphetamines - activate Dopamine, Serotonin, and NE receptors (speed,

    crank)

    f. NE and Serotonin reuptake inhibitors - used to treat depression (Prozac)g. L-Dopa used to treat Parkinson's Disease

    Indolamines - serotonin and histamine

    a. serotonin also derived from tyrosine, different enzymatic pathway

    b. histamine derived from amino acid histidinec. LSD - hallucinogen that blocks Serotonin receptors

    3. Amino Acids - glycine, glutamate, GABA (gamma aminobutyric acid)

    4. Neuropeptides - enkephalins, endorphins, substance P

    a. most are associated with pain regulationb. narcotics (heroin & morphine) - activate enkephalin receptors in brain

    C. Classification by Function

    1. Inhibitory or Excitatory? the action of a neurotransmitter can be either excitatory

    (allow Na+ in) or inhibitory (allow Cl- in), depending on what type of channel itopens

    a. generally inhibitory - glycine & GABA

    b. generally excitatory - glutamatec. some can be either, dependent on location: most other neurotransmitters

    i. ACh - exitatory on skeletal muscle, inhibitory on cardiac muscle

    2. Ionotrophic vs. Metabotrophic Actions

    a. ionotropic - opens Na+ or Cl- channelsb. metabotropic - promote longer lasting changes using "second messenger

    system"

    i. binding of neurotransmitter causes production of intracellular "second

    messenger" called cyclic AMP (cAMP)ii. cAMP can activate enzymes in the cell to alter activity of channels and

    enzymes