Physiology Ch 45 p543-557

Organization of Nervous System, Function of Synapses, and

Neurotransmitters
Central Nervous System Neuron: Basic Functional Unit CNS has 100
billion neurons; signals enter through synapses mostly on dendrites/cell body,
and there may be thousands of connections. Signal leaves via single axon,
which can have many branches
-signal travels in one direction usually down the neuron
Sensory Part of Nervous System Sensory Receptors sensory
experiences excite sensory receptors, such as rods/cones in eye, auditory
receptors in ear, tactile on body, etc
-can elicit immediate reactions from brain or be stored as memories for up to
years
-somatic portion of sensory nervous system transmits sensory information
from receptors of entire body surface and from some deep structures
-and conducts through spinal cord at all levels, reticular substance of
medulla, pons, and mesencephalon, cerebellum, thalamus, and areas
of cerebral cortex
Motor Part of Nervous System Effectors body activities controlled by
contraction of skeletal and smooth muscles, and secretion of active chemicals
by exocrine and endocrine glands; called motor functions of nervous
system and the muscles/glands are called effectors because they perform
the function dictated by the nerves
-the skeletal motor nerve axis for controlling skeletal muscle contraction;
next to this you have another system called the autonomic nervous
system that controls smooth muscles, glands, and other internal body
structures
-skeletal muscles can be controlled from many levels: spinal cord, medulla,
pons, mesencephalon, basal ganglia, cerebellum, and motor cortex
-each of these has its own role: lower areas concerned primarily with
automatic, instantaneous muscle responses to stimuli, and higher
areas with complex movements
Processing of Information most important function of nervous system is
to process incoming information so that appropriate mental and motor
responses occur
-99% of sensory information is discarded by the brain (clothes in contact with
all of body)
-the proper channeling and processing of information in brain is called
integrative function
Role of Synapses in Processing Information synapse is junction point
between neurons, they and determine which direction signals will go
-facilitatory and inhibitory signals from other parts of nervous system can
control transmission; sometimes opening synapses and sometimes closing
them

-some postsynaptic neurons respond with large numbers of output signals,

and some with few, and so synapses perform selective action, blocking out
weak signals while allowing strong ones to a pass, but other times amplifying
weak signals
Storage of Information Memory Most storage occurs in the cerebral
cortex, but the basal region of brain and spinal cord can also store
information
-storage of information is called memory and is a function of synapses
-each time the same signal passes through certain kind of sensory synapses,
the synapses become more capable of transmitting the same signal, called
facilitation, eventually they become so strong that signals within the brain
itself can stimulate these signals to give person feeling of original sensation
without having stimulus
Major Levels of CNS Function CNS separated into spinal cord, lower
brain, and higher brain
Spinal Cord Level neuronal circuits in the cord can cause walking, reflexes
to withdraw body from pain, reflexes that stiffen legs to support body,
reflexes that control blood vessels, GI, urinary excretion
Lower Brain (Subcortical Level) subconscious activities controlled by
these areas medulla, cerebellum, pons, mesencephalon, hypothalamus,
thalamus, and basal ganglia
-subconscious control of arterial pressure and respiration is achieved in
medulla and pons
-control of equilibrium is combined function of cerebellum and reticular
function of medulla, pons, and cerebellum
-feeding reflexes like salivation controlled by medulla, pons, and
mesencephalon
-emotional patterns, anger, excitement, sexual response, pain, pleasure =
cerebral cortex
Higher Brain (Cortical Level) cerebral cortex is a large memory storehouse and never functions alone but always with lower centers of brain
-without cerebral cortex, functions of lower brain centers are often imprecise,
and so cortical functions are to convert imprecise functions to precise
functions
-it is also essential for thought process, but not by itself (lower brain initiates
wakefulness to stimulate cortex)
CNS Synapses infor travels in CNS through nerve impulses between
neurons; each impulse may be blocked in its transmission from one neuron to
the next, it may be changed from single impulse into repetitive imule, and it
may be integrated with other impulses
Types of Synapses: Chemical and Electrical all synapses used for
signal transmission in the CNS are CHEMICAL SYNAPSES, where first neuron
secretes a neurotransmitter at its nerve ending which acts on receptors in
the membrane of the next neuron to excite it, inhibit it, or modify its
sensitivity

-electrical synapses characterized by direct open fluid channels that

conduct electricity from one cell to the next; most of these cells contain gap
junctions to allow free movement of ions between two cells to cause action
potential
One-Way Conduction at Chemical Synapses chemical synapses ALWAYS
travel in one direction: from a presynaptic neuron to a postsynaptic neuron,
via a neurotransmitter
Physiologic Anatomy of the Synapse an anterior motor neuron of the
spinal cord is composed of the soma, an axon, and dendrites
-10000-200000 synaptic knobs called presynaptic terminals lie on the
surfaces of dendrites and soma with 85% of them on dendrites
-these terminals are the ends of nerve fibrils originating from other
neurons
-many presynaptic terminals are excitatory and secrete neurotransmitter to
excite neuron, while other presynaptic terminals are inhibitory and secrete
neurotransmitter to inhibit neuron
Presynaptic Terminals most resemble round/oval knobs
-presynaptic terminal separated from postsynaptic neuron by a synaptic
cleft of 250 angstroms
-terminal has 2 internal structures important for excitatory/inhibitory
functions: transmitter vesicles and mitochondria
-transmitter vesicles contain neurotransmitters to excite or inhibit
neuron after being released into synaptic cleft, depends on what kind
of receptors postsynaptic neuron has
-mitochondria provide ATP to supply new neurotransmitter substance
-an action potential spreads over presynaptic terminal causing depolarization
of membrane and a small number of vesicles to empty into the cleft
-the released neurotransmitters cause an immediate permeability
change, which leads to excitation or inhibition of postsynaptic neuron
Mechanism by Which Action Potential Causes Transmitter Release
from Presynaptic Terminals Role of Calcium presynaptic membrane
has large numbers of voltage-gated calcium channels. A depolarization of
presynaptic membrane causes Ca channels to open and allow large numbers
of Ca ions to flow into terminal
-quantity of neurotransmitters that are released is proportional to number of
Ca ions entering
-Ca entering cell binds proteins on inside surface of membrane called
release sites to open membrane and release vesicle contents
Action of Transmitter Substance on Postsynaptic Neuron Function
of Receptor Proteins post-synaptic membrane has receptors that have 2
major components:
1. binding component protrudes out into cleft to bind
neurotransmitter
2. Ionophore component passes through membrane to interior, and
has 2 types:

a. Ion channel allows passage of specific ions through

membrane
b. Second messenger activator molecule in cytosol that
activates 1 or more substances to increase second messengers
for functions
Ion Channels are of two types: cation (most often Na, or K, or Ca) and
anion (Cl)
-Cation channels that conduct NA are lined with negative charges, which
attract positive Na ions into the channel when channel diameter increases to
allow passage of Na. Those same charges REPEL chloride away
-Anion channels allow passage of Cl when diameter becomes large enough
and block Na, K, Ca
-positively charged sodium going through open cation channels cause
excitement and depolarization; therefore a neurotransmitter needs to be an
excitatory neurotransmitter
-opening Anion channels hyperpolarize membrane and inhibit neuron, caused
by release of inhibitory neurotransmitters
Second Messenger System in Postsynaptic Neuron many processes
like memory require prolonged changes in neurons even after
neurotransmitter is gone; ion channels NOT suitable
-most common second messenger system is G protein receptors
-G protein is attached to cytosolic side of G protein coupled receptor and has
3 components
-the component is the activator, and the components attached
to the . On impulse stimualtoin, alpha portion separates from and
affects intracellular function
-Four changes in neurons that occur in response to alpha subunit are:
1. opening of specific ion channels in membrane these channels (K+)
can stay open long time
2. Activation of cAMP or cGMP in neuron cAMP and cGMP can activate
metabolic machinery in neuron to cause long-term changes in neuron
3. Activation of 1 or more intracellular receptors
4. Activation of gene transcription MOST IMPORTANT; causes formation
of new proteins to change structure or machinery
Excitatory or Inhibitory Receptors in Postsynaptic Membrane some
receptors cause excitation of neuron while others cause inhibition
Excitation 1. opening of Na channels lets positive charges to flow inside of
postsynaptic cell to raise membrane potential in positive direction
toward threshold for excitation
2. depressed conduction through Cl or K channels to decrease diffusion of
Cl ions inside of postsynaptic neuron or K+ out of neuron to make
neuron more excitatory
3. changes to internal metabolism of postsynaptic neuron to excite cell
activity or to decrease number of inhibitory receptors
Inhibition
1. opening of Cl channels in postsynaptic membrane to allow rapid
diffusion of chloride inside making the cell more negative (inhibitory

2. increase in conductance of K ions out of the cell to make it more

negative inside
3. activation of receptor enzymes to inhibit synthesis of excitatory
receptors
Neurotransmitters come in many types: one group is small moleculerapid acting, and the other is large neuropeptides that are slow acting. Small
molecules are for acute responses and neuropeptides are most often for
prolonged signals
Small-Molecule, Rapid Acting Transmitters most often synthesized in
cytosol and absorbed by active transport into vesicles at terminal. After
depolarization, few vesicles are released into cleft within 1ms;
neurotransmitter acts on postsynaptic neuron on ION channels to
increase/decrease conductance
Recycling of Small-Molecule Vesicles vesicles that store and release
small-molecule neurotransmitters are continually recycled for use
-After fusion and transmitter release, vesicle becomes part of synaptic
membrane, but it invaginates again and pinches off to form new vesicle and
then synthesizes new neurotransmitters with enzymes or concentrator
proteins
-Acetylcholine is synthesized in presynaptic terminals from acetyl CoA and
choline through the enzyme choline acetyltransferase then transported
into vesicles
-on release, acetylcholine is cleaved to acetate and choline by
cholinesterase in synaptic cleft and vesicles are recycled; choline is
transported back into presynaptic neuron
Characteristics of Important Small-Molecule Transmitters
1. Acetylcholine secreted by pyramidal cells of motor cortex, basal
ganglia, motor neurons on skeletal muscles, preganglionic neurons of
autonomic nervous system, postganglionic neurons of parasympathetics,
some postganglionics of sympathetics
a. Mostly an excitatory effect, but sometimes inhibitory like inhibition
of heart by vagus nerves
2. Norepinephrine secreted by neurons in brain stem and hypothalamus.
Specifically, norepinephrine-secreting neurons in locus ceruleus in pons
send nerve fibers to brain and help control activity and mood of mind,
such as wakefulness
3. Dopamine secreted by neurons that originate in the substantia nigra,
and terminate in striatal region of basal ganglia dopamine is usually
INHIBITORY
4. Glycine secreted by synapses in spinal cord, ALWAYS INHIBITORY
5. GABA spinal cord, cerebellum, basal ganglia, and cortex ALWAYS
INHIBITORY
6. Glutamate sensory pathways entering CNS ALWAYS EXCITATORY
7. Serotonin secreted by nuclei in median raphe of brainstem and project
to brain and spinal cord areas (dorsal horns) and acts as inhibitory, can
control mood and sleep
8. Nitric Oxide long-term behavior and memory in brain; it is synthesized
as needed and diffuses out of membrane readily. It diffuses inside

postsynaptic neuron and binds to intracellular receptors to cause

metabolic changes that modify excitability
Neuropeptides synthesized as parts of large protein molecules by
ribosomes in soma. Protein molecules enter ER and then to golgi, where
neuropeptide-forming protein is enzymatically split to smaller fragments and
then packaged into minute transmitter vesicles which are released into
cytoplasm
-vesicles are transported to tips of nerve fibers by axonal streaming
cytoplasm, traveling at a low rate and neuropeptides are released after action
potential. Vesicles are NOT recycled
-smaller quantity of neuropeptide needed for response, and they cause more
prolonged action
Electrical Events During Neuronal Excitation
Resting Membrane Potential of Soma resting membrane potential of
spinal motor neuron is about -65mV, whereas peripheral nerve fibers are
around -90mV
-lower voltage is important because it allows both positive and negative
control of degree of excitability
-decreasing voltage to a less negative value makes membrane more
excitable
Concentration Differences of Ions Across Membrane Sodium is high in
extracellular fluid (142mEq/L) but low in extracellular fluid, indicating there
exists a Na/K pump that pumps K+ to the interior
-Chloride is high in extracellular fluid but low inside neuron; the -65mV inside
neuron repels chloride ions to keep them on the outside
-Nernst Potential: EMF = +/-61 * log (conc. Inside/conc. Outside)
-calculates potential of ions to be in or out of membrane: Na constantly
leaks in but is pumped out, K constantly leaks out but is pumped in, Cl
leaks inside slightly
Uniform Distribution of Electrical Potential Inside Soma intracellular
fluid of soma is highly conductive, and diameter of soma is large, causing no
resistance to conduction of current; any change in potential in fluid causes
equal change in potential at all other points in soma
-plays a role in summation of signals
Effect of Synaptic Excitation on Postsynaptic Membrane Excitatory
Postsynaptic Potential excitatory neurotransmitter acts on receptor to
increase membrane permeability to Na, sodium ions diffuse inside due to
large concentration gradient
-rapid influx neutralizes part of negativity of resting membrane potential from
-65 to -45 millivolts
-a positive increase in voltage above resting membrane potential is
called excitatory postsynaptic potential (EPSP); if it rises high
enough it will elicit action potential
-increase from -65 to -45 requires simultaneous discharge of many terminals
(40-80) to produce this increase in potential; this is called summation

Generation of Action Potentials in Initial Segment of Axon Leaving

Neuron Threshold- when EPSP rises high enough, it initiates action
potential. It does not begin next to excitatory synapses but rather at the
initial segment of axon because soma has few voltage gated Na channels,
but membrane of initial axon segment has 7x as many voltage gated Na
channels and can generate action potential
-EPSP on axon needs to be +10-20mV, on soma it needs to be +30-40 for
action potential
-once action potential begins, it travels across axon and backward through
soma
-threshold is usually -45mV
Electrical Events During Inhibition
Effect of Inhibitory Synapses on Postsynaptic Membrane inhibitory
synapses open chloride channels to allow easy passage. Nernst potential for
Cl is -70mV which is more negative than -65mV inside membrane, and so
opening Cl channels will make interior more negative
-opening of K channels will allow K+ ions to move out of the cell to make
interior membrane more negative
-Cl influx and K efflux causes hyperpolarization to inhibit neuron because it
is more negative
-a decrease in resting membrane potential is called inhibitory postsynaptic
potential (IPSP)
Presynaptic Inhibition in addition to postsynaptic inhibition caused by
inhibitory synapses, an inhibition occurs at presynaptic terminals before
signal reaches synapse, called presynaptic inhibition caused by release of
inhibitory substance onto outsides of presynaptic nerve before their own
endings terminate on postsynaptic neuron
-inhibitory substance is usually GABA which opens anion channels, allowing
Cl to diffuse in and cancel excitatory effect of Na ions entering when action
potential arrives
-presynaptic inhibition occurs in many sensory pathways
Time Course of Postsynaptic Potentials when excitatory synapse
excites anterior motor neuron, membrane becomes permeable to Na for 12ms when enough Na diffuses inside to create EPSP, which will decline if no
action potential is reached
-opposite occurs if an IPSP increase permeability of membrane to potassium
or chloride for 1-2ms to decrease intraneural potential to a more negative
value
Spatial Summation Threshold for Firing many presynaptic terminals
are stimulated at the same time, and when their signal spreads over wide
areas on a neuron, the effects can summate and add to one another until
excitation does occur
-each excitatory synapse that discharges simultaneously and total intrasomal
potential becomes more positive than just a 0.5-1mV (one terminal release)

-when EPSP becomes large enough, a threshold for firing will be reached and
an action potential will develop
-effect of summing simultaneous postsynaptic potentials is called spatial
summation
Temporal Summation Caused by Successive Discharges of
Presynaptic Terminal every time presynaptic terminal firs, the transmitter
opens membrane channels for a ms, but the changed postsynaptic potential
lasts up to 15ms after channels have closed; so a second opening of the
same channels can increase potential to a greater level; multiple discharges
from a single terminal is called temporal summation
-Simultaneous Summation of EPSP and IPSP if you add the potential
differences caused by IPSP, and EPSP for a net difference, you can nullify
signal, so to excite you need stronger EPSP
Facilitation of Neurons the summated postsynaptic potential is not high
enough for threshold, but the neuron is said to be facilitated, where
membrane is closer to threshold, and another excitatory signal can excite
neuron easily
Special Function of Dendrites for Exciting Neurons Dendrites have a
large special field of excitation, and extend in all directions from soma- they
receive signals from large spatial area to provide vast opportunity for
summation
-80-95% of all presynaptic terminals of anterior motor neuron terminate on
dendrites
Most Dendrites Cannot Transmit Action Potentials most dendrites
cannot transmit potential because they dont have voltage gated sodium
channels, but the DO transmit electrotonic current down dendrites to soma
(direct spread of current by ion conduction in fluids)
Decrement of Electrotonic Conduction in Dendrites Greater
Excitatory or Inhibitory Effect by Synapses Near Soma membrane
potential gets more negative as you move from extremity of dendrite to the
soma
-large share of EPSP is lost before it reaches soma because dendrites are long
and membranes are thin and partially permeable to K and Cl, making tem
leaky
-before excitatory potential can reach soma, large amount is lose by
leakage
-the decrease in potential as it spreads is called decremental conduction
Summation of Excitation and Inhibition in Dendrites dendrites can
summate excitatory and inhibitory postsynaptic potentials
-inhibitory segments on axon hillock provide powerful inhibition because it
has direct effect of increasing threshold for excitation where action potential
is generated
Relation of State of Excitation to Rate of Firing

Excitatory State defined as summated degree of excitatory drive of

neuron, happens when there is a higher degree of excitation than inhibition; if
opposite, called inhibitory state
-when excited state rises above threshold, neuron will fire repetitively as long
as excitatory state remains at that level
-some CNS neurons fire continuously because normal excitatory state is
above threshold, but the frequency of firing can change depending on
changing excitatory state
Some Special Characteristics of Synaptic Transmission
Fatigue of Synaptic Transmission when excitatory synapses are
repetitively stimulated, number of discharges is great, but firing rate
becomes less over time, called fatigue
-areas of overexcitement can trigger fatigue, which causes neurons to lose
excitability
-mechanism of fatigue is exhaustion of stores of neurotransmitter in
presynaptic terminals, but can also happen from progressive inactivation of
postsynaptic membrane receptors and abnormal ion concentrations inside
postsynaptic cell
Effect of Acidosis/Alkalosis on Transmission most neurons are
responsive to pH changes
-Alkalosis INCREASES neuronal excitability and can cause epileptic seizures
-Acidosis causes DEPRESSION of neuronal activity
Effect of Hypoxia on Transmission cessation of O2 for a few seconds
can cause complete inexcitability of some neurons
Effects of Drugs on Transmission drugs that increase excitability are
caffeine, theophylline, and theobromine (in tea, coffee, cocoa) does this by
reducing threshold
-strychnine is best known agent to increase excitability by inhibiting action
of normally inhibitory neurotransmitters, especially effect of glycine on cord
-most anesthetics increase neuronal membrane threshold for activation
Synaptic Delay during transmission of signal between neurons, amount of
time consumed in the process of discharge of transmitter by terminal,
diffusion of transmitter to postsynaptic membrane, action of transmitter on
membrane, action of receptor to increase permeability, inward diffusion of Na
to raise excitatory postsynaptic potential to high enough level to elicit action
potential
-the minimal period of time required is 0.5s for all these events, called
synaptic delay