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 store-house 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 α component is the activator, and the βγ components attached to the α. On
impulse stimualtoin, alpha portion separates from βγ 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 molecule-rapid 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 1-2ms 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 12ms 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 don’t 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