Los Angeles Mission College



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

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II. The Structure of a Neuron (Nerve Cell)

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

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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

d. oligodendrocytes - form "myelin sheaths" around axons of CNS; increase speed of impulses

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2. Support Cells of the PNS

a. Schwann cells - form "myelin sheaths" around axons; assist in regeneration of axon

b. satellite cells - control chemical environment

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C. Special Characteristics of Neurons

1. amitotic - "not mitotic"; most 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

a. receptive/input component of the neuron; incoming signals are forwarded to the cell body

b. 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) = 1/1000 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 separation of charge, 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)

C. 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

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D. 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

2. K+ Leak Channels K+ leaks out of the cell

3. Cl- level [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.

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B. resting membrane potential – voltage when the cell is at rest = ~ -70 mv (-20 to -200)

V. Membrane Potential and Signaling

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

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 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 effected 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. allow 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 bind to chemically-gated ion channels on the postsynaptic cell.

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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)

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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 to 10,000 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 (-100mv), 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 (timing) and spatial summation (location) 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.

Summation of EPSP’s and IPSP’s at axon hillock determine if action potential will occur.

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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.

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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 than100 neurotransmitters 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.

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B. Classification by Chemical Structure

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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 aceytalcholinesterase

g. some snake/spider venoms - block ACh receptor

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h. muscarinic receptors – stimulated by muscarin (mushroom poison); smooth and cardiac muscle

i. nicotinic receptors – stimulated by nicotine; motor endplate of skeletal muscle cells; brain – attention, learning, memory; curare – blocks ACh at neuromuscular junction; botox – muscle relaxant

j. Alzheimer’s disease – loss of cholinergic neurons responsible for memory; cholinesterase inhibitors responsible for more ACh available

2. Biogenic Amines

catecholamines - dopamine, norepinephrine (NE), and epinephrine (derived from amino acid tyrosine)

a. common biosynthetic pathway

b. enzymes determine final product in neuron

c. tyrosine is precursor to all of these

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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

h. monoamine oxidase – breaks down in the synaptic cleft (inhibitors as antidepressants)

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i. dopamine –

nigrostriatal pathway – motor function (Parkinson’s disease is loss of cells)

mesolimbic pathway – thought and reward (Schizophrenia is too much dopamine release) (also associated with addiction)

j. norepinephrine – sympathetic n.s. uses on smooth muscle; cardiac muscle and glands

Indolamines - serotonin and histamine

a. serotonin also derived from tyrosine, different enzymatic pathway; implicated in mood, behavior, and appetite; serotonin reuptake inhibitors used to treat depression

b. histamine derived from amino acid histidine

c. LSD - hallucinogen that activates Serotonin receptors

Broadly distributed in the brain; emotions and biological clock; associated with mental illness

3. Amino Acids –

i. glutamate – most important excitatory neurotransmitter in the brain; all serve as ion channels; 80% of synapses in cerebral cortex; 3 types of receptors: NMDA, AMPA, (both memory storage), Kainate

synaptic plasticity – repeated use of that pathway may strengthen or weaken it

long term potention (LTP) – repeated stimulation enhances excitability; found in hippocampus of the brain where memories are stored; associated with NMDA and AMPA receptors

long term depression (LTD) – glutamate-releasing neurons stimulate release of endocannibinoids

ii. glycine (inhibitory) – produces IPSP’s; opens Cl- channels; allows antagonistic muscle groups to relax; relaxation of the diaphragm for breathing; strychnine poison that stops breathing

iii. GABA (gamma aminobutyric acid) – used by 1/3 of brain neurons; inhibitory opening Cl- channels; degeneration of neurons in cerebellum causes Huntington’s disease

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4. Neuropeptides – endogenous opioids, oxytocin, tachykinins, ekephalins, endorphins, substance P

a. substance P – mediator of pain signals

b. endorphins – natural opiates – reduce pain signals

c. narcotics (heroin & morphine) - activate enkephalin receptors in brain

d. opioids – drugs that bind to these receptors are for pain relief

e. endogenous opioids – polypeptides produced by brain and pituitary gland

f. endocannabinoids – binds to marijuana agent THC; rapid heart rate, increased blood pressure, increased breathing rate, increased appetite (“the munchies”), slowed reaction time

5. Miscellaneous – nitric oxide, purines (e.g. adenosine and ATP)

a. nitric oxide – gas produce by some neurons of the PNS and CNS; activates production of cGMP as second messenger; secreted by autonomic neurons in digestive tract, respiratory tract, and penis causing muscle relaxation; responsible for erection (Viagra)

C. Classification by Function

1. Agonist – stimulates the receptor

2. Antagonist – blocks the receptor

3. Inhibitory or Excitatory? - the action of a neurotransmitter can be either excitatory (allow Na+ in) or inhibitory (allow Cl- in or K+ out), depending on what type of channel it opens

a. generally inhibitory - glycine & GABA

b. generally excitatory - glutamate

c. some can be either, depending on location : most other neurotransmitters

i. ACh - exitatory on skeletal muscle

inhibitory on cardiac muscle

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