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, joints
b. visceral afferents - from membranes & organs

2. Motor (Efferent) Division - FROM the CNS

a. Somatic Nervous System (Voluntary) - to skeletal muscles
b. 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 environment
around neurons and selective transport
from capillaries
b. microglia -eat infectious microbes of CNS
c. 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 in

regeneration 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

 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 diameter
2. single large spherical nucleus with nucleolus
3. Nissl Bodies - Rough Endoplasmic Reticulum (rER); make proteins and
plasma membrane
4. 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 body
signals 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 PNS
c. 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 triggered
e. axon collaterals- rare branches of an axon
f. telodendria - typical terminal branches of an axon which may number
up to 15,000
g. 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 knobs
ii. 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
 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 and
one axon (throughout the CNS)

2. bipolar neuron - have two (bi) processes: one dendrite and one axon, each
extending 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
extension
a. 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 TOWARD

the 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 voltage

less charge separated = smaller voltage

2. volts - units of voltage

millilvolt (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, the

more "potential energy" for current to move
 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 current

DECREASED 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 across
membrane

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

1. electrical gradient - positive charges move

toward negative charges and vice versa
2. 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+]in
K+ leaks out of the cell
2. K+ Leak Channels
 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 mV0 mV+20 mV +60 mV

2. hyperpolarization - inside of the cell becomes even more negative; the resting
membrane 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 distances
from 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 the

“postsynaptic” 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, causing
further 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.
 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 action
potential.

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 (# per

second) 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 to

generate another action potential

G. Relative Refractory Period - when Na+ channels are closed, and K+ channels
regenerate 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 impulse

2. 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.)
 1. axodendritic - axon terminal -> dendrite
2. axosomatic - axon terminal -> neuron cell body
3. axonaxonic - axon terminal -> another axon
4. dendrodendritic - dendrite -> dendrite
5. dendrosomatic - dendrite -> neuron cell body
6. neuromuscular junction - axon terminal -> muscle
7. neuroglandular junction - axon terminal ->gland
8. presynaptic neuron - "before" the synapse; the neuron that is sending the signal
9. 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 the
postsynaptic 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 its
concentration gradient

3. Increased Ca++ Causes Neurotransmitter Release - As Ca++ increases in the axon

terminal, synaptic vesicles containing the neurotransmitter fuse with the plasma
membrane, releasing contents into the synaptic cleft

4. Neurotransmitter Binds Receptor - Opens Ion Channels - The released

neurotransmitter 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 Action

Potentials

EPSPs result when a neurotransmitter opens Na+ channels, causing depolarization of the
cell body, and increased likelihood of generating an axon potential. EPSPs are graded
potentials, 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
 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 of
generating 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 EXCITATORY
and 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 or
more
2. more than 100 neurotransmitters are known
3. Neurotransmitters may be synthesized in the axon terminal, or in the cell body
and 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 enzyme
d. 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
 2. Biogenic Amines

catecholamines - dopamine, norepinephrine (NE), and epinephrine

a. common biosynthetic pathway

b. 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 histidine
c. 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 regulation

b. 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 it
opens

a. generally inhibitory - glycine & GABA

b. generally excitatory - glutamate
c. 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- channels

b. 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