Download phys chapter 45 [10-24

Phys Ch 45
General Design of the Nervous System
 When important sensory info excites the mind, it is immediately channeled into proper integrative and motor
regions of brain to cause desired response (integrative function of nervous system)
 Synapses perform selective action, blocking weak signals while allowing strong signals to pass; can select and
amplify weak signals; can channel in one direction or many
 Most storage occurs in cerebral cortex, but basal regions of brain and spinal cord can store small amounts
o Most important sensory info stored
o Each time certain types of sensory signals pass through sequences of synapses, these synapses become
more capable of transmitting same type of signal next time (facilitation)
o After sensory signals have passed through synapses enough times, synapses become so facilitated that
signals generated within brain itself can cause transmission of impulses through same sequences of
synapses, even when sensory input not excited (re-experiencing older sensations as memories)
 Once memories stored, they become part of brain processing mechanism for future thinking (thinking processes
of brain compare new sensory experiences with stored memories; memories help select important new sensory
info and channel this into appropriate memory storage areas for future use or into motor areas to cause
immediate bodily responses
Major Levels of Central Nervous System Function
 Neuronal circuits in cord (without any input from brain whatsoever; severed spinal cord) can cause walking
movements, reflexes that withdraw portions of body from painful objects, reflexes that stiffen legs to support
body against gravity, and reflexes that control local blood vessels, GI movements, or urinary excretion
o Upper levels of nervous system often operate by sending signals to control centers of cord, commanding
the cord center to perform its function
 Subconscious control of arterial pressure and respiration achieved mainly in medulla and pons
 Control of equilibrium combined function of older portions of cerebellum and reticular substance of medulla,
pons, and mesencephalon
 Feeding reflexes (salivation and licking lips in response to taste of food) controlled by medulla, pons,
mesencephalon, amygdala, and hypothalamus
 Emotional patterns, reaction to pain, sexual response, etc., can still occur after destruction of much of cortex
 Cortex never functions alone but always in association with lower centers of nervous system
o Cortical info converts functions of lower brain centers to determinative, precise operations
o Essential for most thought processes
o Depends on lower brain centers that establish such things as wakefulness
Central Nervous System Synapses
 Synaptic functions of neurons – blocking, changing, or integrating APs as they are passed to successive neurons
 Almost all synapses used for signal transmission in CNS are chemical synapses
 Electrical synapses characterized by direct open fluid channels that conduct electricity from one cell to the next
o Most consist of small protein tubular structures (gap junctions) that allow free movement of ions from
interior of one cell to interior of next
o How APs get transmitter from one smooth muscle fiber to next in visceral smooth muscle
o Also used in cardiac muscle
 Conduction of chemical synapses often unidirectional; conduction of electrical synapses often bidirectional
 Presynaptic terminal has lots of mitochondria to provide ATP, which supplies energy for synthesizing new
transmitter substance
o Presynaptic membrane contains large numbers of voltage-gated Ca2+ channels; when AP depolarizes
membrane, Ca2+ channels open and allow large amounts of Ca2+ to flow into terminal
o Quantity of neurotransmitter released from terminal into synaptic cleft directly related to number of
Ca2+ ions that enter
o When Ca2+ enters presynaptic terminal, they bind with protein molecules on inside surface of membrane
(release sites); binding causes release sites to open through membrane, allowing transmitter vesicles to
release transmitter into cleft after each single AP
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Postsynaptic receptor proteins composed of binding component (binds neurotransmitter) and ionophore
component (passes through membrane to interior)
o Ionophore can be ion channel (allows passage of specified types of ions through PM) or second
messenger activator (activates substance inside postsynaptic neuron)
 Ion channels can be cation channels (mostly Na+, but can be K+ or Ca2+) or anion channels (Cl-)
 Cation channels lined with negative charges that attract the cation into the channel
when the channel diameter increases to size larger than that of their ion; excitatory
transmitters open these
 Anion channels mostly size permissive (cations larger than anions, so they can’t fit);
inhibitory transmitters open these
 When transmitter substance activates channel, it opens fast; when transmitter
substance no longer present, channel closes fast
 Second messenger system used for processes such as memory that require prolonged changes
in neurons for seconds to months after initial transmitter substance gone
 G-proteins – attached to interior portion of receptor; consists of αβγ complex; on
activation, α portion separates and is free to move in cytoplasm of cell, where it opens
specific ion channels, activates cAMP or cGMP, activates intracellular enzymes, or
activates gene transcription (used for long-term memory process)
Excitation – opening of Na+ channels allow large numbers of cations into postsynaptic cell; raises intracellular
membrane potential in positive direction (depolarization)
o Depressed conduction through Cl- or K+ channels or both; decreases diffusion of Cl- to inside of
postsynaptic neuron or decreases diffusion of K+ out of neuron; effect is to make internal membrane
more positive than normal, just in a slower fashion
o Changes in internal metabolism of postsynaptic neuron to excite cell activity or increase number of
excitatory membrane receptors or decrease number of inhibitory membrane receptors
Inhibition – opening of Cl- channels through postsynaptic neuronal membrane; allows rapid diffusion of anions
inside, hyperpolarizing cell
o Increase in conductance of K+ out of neuron
o Activation of receptor enzymes that inhibit cellular metabolic functions that increase number of
inhibitory synaptic receptors or decrease number of excitatory receptors
Small-molecule transmitters cause most acute responses of nervous system (transmission of sensory signals to
brain and motor signals back to muscles); mostly synthesized in cytosol of presynaptic terminal and absorbed by
active transport into transmitter vesicles in terminal
o Most often affects ion channel receptor types on postsynaptic terminal
Neuropeptides usually cause more prolonged actions
Vesicle portion of membrane invaginates back to inside of presynaptic terminal to be recycled; new vesicular
membrane still contains appropriate enzyme proteins or transport proteins required for synthesizing and/or
concentrating new transmitter substance inside vesicle
In presynaptic terminal, ACh synthesized from acetyl-CoA and choline in presence of choline acetyltransferase
and is then transported into specific vesicles
o When vesicles release ACh into synaptic cleft during signal transmission, ACh rapidly split again to
acetate and choline by cholinesterase (present in proteoglycan reticulum that fills space of synaptic cleft
o Inside presynaptic terminal, vesicles recycled; choline actively transported back into presynaptic
terminal to be used for synthesis of new ACh
Acetylcholine used by terminals of large pyramidal cells from motor cortex, several different types of neurons in
basal ganglia, motor neurons that innervate skeletal muscles, preganglionic neurons of ANS, postganglionic
neurons of PNS, and some postganglionic neurons of SNS
o Usually excitatory (inhibitory at heart by vagus nerves)
Norepinephrine used by many neurons with cell bodies in brainstem and hypothalamus
o Norepi-secreting neurons in locus ceruleus in pons send nerve fibers to widespread areas of brain to
help control overall activity and mood of mind (increasing level of wakefulness)
o Secreted by most postganglionic neurons of SNS (can excite or inhibit organs)
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Dopamine secreted by neurons that originate in substantia nigra; termination of neurons mainly in striatal
region of basal ganglia; usually inhibitory
Glycine secreted mainly at synpases in spinal cord; inhibitory transmitter
GABA secreted by nerve terminals in spinal cord, cerebellum, basal ganglia, and many areas of cortex; inhibitory
Glutamate secreted by presynaptic terminals in many sensory pathways entering CNS and many areas of CNS;
excitatory transmitter
Serotonin secreted by nuclei that originate in median raphe of brainstem and project to many brain and spinal
cord areas, especially dorsal horns of spinal cord and hypothalamus
o Inhibitor of pain pathways in cord, inhibitory in higher regions of nervous system to control mood
NO secreted by nerve terminals in area of brain responsible for long-term behavior and memory; not preformed
or stored in vesicles; synthesized as needed and diffuses out of presynaptic terminals and into postsynaptic
o Usually doesn’t greatly alter membrane potential; changes intracellular metabolic functions that modify
neuronal excitability
Neuropeptides synthesized as integral parts of large-protein molecules by ribosomes in neuronal cell body
o Protein molecules enter spaces inside ER and Golgi apparatus, where it is split into smaller fragments
and packaged into transmitter vesicles that are released into cytoplasm
o Transmitter vesicles transported to tips of nerve fibers by axonal streaming of axon cytoplasm
o Vesicles release transmitter at neuronal terminals in response to APs like small-molecule transmitters
o Vesicles autolyzed, not reused
o Much smaller quantities of neuropeptides released than small-molecule transmitters (more potent)
Na+ high in extracellular fluid but low inside neuron; caused by strong somal membrane Na+ pump that
continually pumps Na+ out of neuron
K+ high inside neuronal soma but low in extracellular fluid because of Na+/K+ exchanger
Cl- high in extracellular fluid but low in neuron; membrane somewhat permeable to Cl- and may be weak Clpump; mostly low in concentration because resting potential slightly negative, forcing Cl- out through pores until
concentration much less inside than outside
Nernst potential (EMF) – potential on inside of membrane that exactly opposes movement of an ion (potential
negative for positive ions and positive for negative ions)
Intracellular fluid of neuron highly conductive electrolytic solution; diameter of neuronal soma large, causing
almost no resistance to conduction of electric current; any change in potential in any part of intrasomal fluid
causes almost exactly equal change in potential at all other points in soma as long as neuron not transmitting AP
o Plays role in summation of signals entering neuron from multiple sources
Excitatory postsynaptic potential (EPSP) – positive increase in voltage above resting potential; measured as
difference between it and resting potential (EPSP of +20 would be increasing a normal cell with resting potential
-65 to -45); any large change in resting potential requires simultaneous discharge of many terminals
When EPSP surpasses threshold, AP begins at initial segment of axon where it leaves neuronal soma (not where
excitatory synapses are)
o Soma has relatively few voltage-gated Na+ channels in its membrane, making it difficult for EPSP to open
required number of channels to elicit AP
o Membrane of initial segment of axon has 7x as many voltage-gated Na+ channels as soma and can
generate AP with much greater ease
o Once AP begins, it travels peripherally along axon and backward into dendrites (doesn’t get far because
dendrites don’t have many voltage-gated Na+ channels)
Inhibitory synapses open mainly Cl- channels; increase in negativity beyond normal resting potential is inhibitory
postsynaptic potential (IPSP)
Presynaptic inhibition caused by release of inhibitory substance onto outsides of presynaptic nerve fibrils before
their own endings terminate on postsynaptic neuron; in most cases, inhibitory transmitter substance is GABA
o Opens anion channels that inhibit synaptic transmission because they cancel much of excitatory effect of
cations that also enter terminal fibrils when AP arrives
o Occurs in many sensory pathways
o Adjacent sensory nerve fibers often mutually inhibit one another, minimizing sideways spread and
mixing of signals in sensory tracts
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When excitatory synapse excites anterior motor neuron, neuronal membrane becomes highly permeable to Na+
for short time; creates EPSP which declines over time because of positive charges leaking out
 IPSP increases permeability of membrane to K+ and Cl- for short time, causing more negative potential
 Spatial summation – simultaneous postsynaptic potentials by activating multiple terminals on widely spaced
areas of neuronal membrane add up to create cellular response (AP or not)
 Temporal summation – rapid firing of few postsynaptic receptors opening channels for a little at a time adds up
(takes a while for cations to diffuse out every time)
 Facilitation – when summated postsynaptic potential excitatory but hasn’t risen high enough to reach threshold
 Most dendrites fail to transmit APs because membranes have relatively few voltage-gated Na+ channels, but
they do transmit electrotonic current down dendrites to soma (direct spread of electoral current by ion
conduction in fluids)
 Dendrites can have high levels of EPSP but most of this lost before it reaches soma because dendrites long and
membranes thin and partially permeable to K+ and Cl-, making them leaky to electric current (decremental
conduction); the farther the excitatory synapse from the soma, the greater the decrement
 Excitatory state of neuron – summated degree of excitatory drive to that neuron; when excitatory state of
neuron rises above threshold, it will fire repetitively as long as excitatory state remains at that level
 Some neurons in CNS fire continuously because normal excitatory state above threshold level; frequency of
firing can be increased by further increasing excitatory state
Some Special Characteristics of Synaptic Transmission
 Fatigue – when excitatory synapses repetitively stimulated at rapid rate, number of discharges by postsynaptic
neuron at first very great but firing rate slowly decreases
o When areas of nervous system become overexcited, fatigue causes them to lose excess excitability for a
while; this is how a seizure eventually ceases
o Caused by exhaustion of stores of transmitter substance in presynaptic terminals, progressive
inactivation of many postsynaptic membrane receptors, and slow development of abnormal
concentrations of ions inside postsynaptic neuronal cell
 Normally alkalosis greatly increases neuronal excitability; acidosis greatly depresses neuronal activity
 Neuronal excitability highly dependent on adequate supply of oxygen (don’t fire if no O2)
 Caffeine, theophylline, and theobromine increase excitability of neurons by reducing threshold for excitation
 Strychnine increases excitability of neurons by inhibiting action of some normally inhibitory transmitter
substances, especially glycine in spinal cord; results in severe muscle spasms
 Most anesthetics increase neuronal threshold and thereby decrease synaptic transmission at many points
o Many anesthetics especially lipid soluble, so they change physical characteristics of neuronal
membranes, making them less responsive to excitatory agents
 Synaptic delay – minimal period of time required for events of excitation and AP firing to take place