Lecture: Neurophysiology
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 mV0 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