NP550 Functional Neuroanatomy

Neural Communication: An Overview

Before we begin our discussion of the action potential, let’s step back and see how neurons can interact to produce a useful behavior.
We begin by examining a simple assembly of three neurons and a muscle that controls a withdrawal reflex. In the next two figures (and
in subsequent figures that illustrate simple neural circuits), neurons are depicted in shorthand fashion as several-sided stars. The
points of these stars represent dendrites, and only one or two terminal buttons are shown at the end of the axon. The sensory neuron
in this example detects painful stimuli. When its dendrites are stimulated by a noxious stimulus (such as contact with a hot object), it
sends messages down the axon to the terminal buttons, which are located in the spinal cord. (See Figure 2.12.) The terminal buttons of
the sensory neuron release a
neurotransmitter that excites the
interneuron, causing it to send
messages down its axon. The
terminal buttons of the
interneuron release a
neurotransmitter that excites the
motor neuron, which sends
messages down its axon. The axon
of the motor neuron joins a nerve
and travels to a muscle. When the
terminal buttons of the motor
neuron release their
neurotransmitter, the muscle
cells contract, causing the hand to
move away from the hot object.

So far, all of the synapses have had excitatory effects. Now let us complicate matters a bit to see the effect of inhibitory synapses.
Suppose you have removed a hot drink from the microwave. As you pick up the cup, the heat from the drink burns your hand. The pain
caused by the heat triggers a withdrawal reflex that tends to make you drop the cup. Yet you manage to keep hold of it long enough to
get to a table and put it down. What prevented your withdrawal reflex from making you drop the cup on the floor? The pain from the
hot cup increases the activity of excitatory synapses on the motor neurons, which tends to cause the hand to pull away from the cup.
However, this excitation is counteracted by inhibition, supplied by another source: the brain. The brain contains neural circuits that
recognize what a disaster it would be if you dropped the cup on the floor. These neural circuits send information to the spinal cord that
prevents the withdrawal reflex from making you drop the cup. Figure 2.13 shows how this information reaches the spinal cord. As you
can see, an axon from a neuron in the brain reaches the spinal cord, where its terminal buttons form synapses with an inhibitory
interneuron. When the neuron in the brain becomes active, its terminal buttons excite this inhibitory interneuron. The interneuron
releases an inhibitory neurotransmitter, which decreases the activity of the motor neuron, blocking the withdrawal reflex. This circuit
provides an example of a contest between two competing tendencies: to drop the cup and to hold onto it. Of course, reflexes are more
complicated than this description,
and the mechanisms that inhibit
them are even more so. Thousands of
neurons are involved in this process.
The neurons shown in Figure 2.13
represent many others: Dozens of
sensory neurons detect the hot
object, hundreds of interneurons are
stimulated by their activity,
hundreds of motor neurons produce
the contraction—and thousands of
neurons in the brain must become
active if the reflex is to be inhibited.
Yet this simple model provides an
overview of the process of neural
communication, which is described
in more detail below.

Conduction of the Action Potential

Moving from a basic description of the resting membrane potential and the production of the action potential, let’s next consider the
movement of the message down the axon, or conduction of the action potential. As the action potential travels, it remains constant in
size. This experiment establishes a basic law of axonal conduction: the all-or-none law. This law states that an action potential either
occurs or does not occur, and, once triggered, it is transmitted down the axon to its end. An action potential always remains the exact
same size, without growing or diminishing. And when an action potential reaches a point where the axon branches, it splits but does
not diminish in size. An axon will transmit an action potential in either direction, or even in both directions, if it is started in the middle
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of the axon’s length. However, because action potentials in living animals start at the end attached to the soma, axons normally carry
one-way traffic. The strength of a muscular contraction can vary from very weak to very forceful, and the strength of a stimulus, like
light detected by the neurons in the eye, can vary from barely detectable to very intense. Action potentials in axons control the strength
of muscular contractions and represent the intensity of a physical stimulus. But if action potentials are all-or-none events and every
action potential is exactly the same size, how can they represent information that can vary in a continuous fashion, such as strong to
weak muscle contraction, or bright to dim light? The answer is surprising: Variable information is represented by an axon’s rate of firing
action potentials. A high rate of firing causes a strong muscular contraction, and a strong stimulus (such as a bright light) causes a high
rate of firing in axons that serve the eyes. For example, an axon might respond to a dim light such as a candle by firing 10 identical
action potentials in a unit of time (a low rate of firing). The same axon might respond to a bright floodlight by firing 100 identical action
potentials in the same unit of time (a high rate of firing). The rate law refers to the principle that variations in the intensity of a stimulus
or other information being transmitted in an axon are represented by variations in the rate at which the axon fires (see Figure 2.19).
By analogy, imagine that every time you clap your hands, the sound occurs at the exact same volume. To show your enthusiasm for a
great performance you might clap your
hands very quickly for 30 seconds (a high
rate of firing). To show your response to
a performance you didn’t enjoy as much,
you might only clap your hands a few
times, slowly, for 30 seconds (a low rate
of firing). You are using the same method
of communication (clapping, or in the
case of a neuron, firing action potentials),
but you are varying the rate to convey
different messages.

Recall that all but the smallest axons in mammalian nervous systems are myelinated; segments of the axons are covered by a myelin
sheath produced by the oligodendrocytes of the CNS or the Schwann cells of the PNS. These segments are separated by portions of
naked axon, the nodes of Ranvier. Conduction of an action potential in a myelinated axon is somewhat different from conduction in an
unmyelinated axon. Schwann cells and the oligodendrocytes of the CNS wrap
tightly around the axon, leaving no measurable extracellular fluid between them
and the axon. The only place where a myelinated axon comes into contact with the
extracellular fluid is at a node of Ranvier, where the axon is exposed to the
extracellular fluid. In the myelinated areas there can be no inward flow of Na+ when
the sodium channels open because there is no extracellular sodium. The axon
conducts the electrical disturbance from the action potential to the next node of
Ranvier. The disturbance is conducted passively, the way an electrical signal is
conducted through an insulated cable. The disturbance gets smaller as it passes
down the axon, but it is still large enough to trigger a new action potential at the
next node. This decrease in the size of the disturbance is called decremental Figure 2.19a
conduction (i.e., the decrease in the amplitude of an electric impulse as it travels
along a nerve fiber; see figure 2.19a). The action potential gets retriggered, or
repeated, at each node of Ranvier, and the electrical disturbance that results is
conducted decrementally along the myelinated area to the next node. Transmission
of this message, hopping from node to node, is called saltatory conduction. (See
Figure 2.20.) Saltatory conduction confers two advantages. The first is economic.
Sodium ions enter axons during action potentials, and these ions must eventually be
removed. Sodium– potassium transporters must be located along the entire length
of unmyelinated axons because Na+ enters everywhere. However, because Na+ can
enter myelinated axons only at the nodes of Ranvier, much less gets in, and
consequently much less has to be pumped out again. Therefore, myelinated axons
expend much less energy to maintain their sodium balance. The second advantage
to myelin is speed. Conduction of an action potential is faster in a myelinated axon
because the transmission between the nodes is very fast. Increased speed enables an animal to react faster and (undoubtedly) to think
faster. One of the ways to increase the speed of conduction is to increase size. Because it is so large, the unmyelinated squid axon, with
a diameter of 500 μm, achieves a conduction velocity of approximately 35 m/sec (meters per second). However, a myelinated cat axon
achieves the same speed with a diameter of a mere 6 μm. The fastest myelinated axon, 20 μm in diameter, can conduct action potentials
at a speedy 120 m/sec, or 432 km/h (kilometers per hour). At that speed a signal can get from one end of an axon to the other without
much delay.

Communication Between Neurons

Now that you have encountered information about the basic structure of neurons and the nature of the action potential, it is time to
examine the ways in which neurons can communicate with each other. These communications make it possible for circuits of neurons
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to gather sensory information, make plans, and initiate behaviors. The primary means of communication between neurons is synaptic
transmission—the transmission of messages from one neuron to another across a synapse. As we saw, these messages are carried by
neurotransmitters, released by terminal buttons of the sending, or presynaptic cell. These chemicals diffuse across the fluid-filled gap
between the terminal buttons and the membranes of the neurons with which they form synapses, called the postsynaptic cell.
Neurotransmitters then produce postsynaptic potentials—brief depolarizations or hyperpolarizations—that increase or decrease
the rate of firing of the axon of the postsynaptic neuron. Neurotransmitters exert their effects on cells by attaching to a particular region
of a receptor molecule called the binding site. A molecule of the chemical fits into the binding site the way a key fits into a lock: The
shape of the binding site and the shape of the molecule of the neurotransmitter are complementary. A chemical that attaches to a
binding site is called a ligand. Neurotransmitters are naturally occurring ligands, produced and released by neurons. But other
chemicals found in nature (primarily in plants or in the poisonous venoms of animals) can serve as ligands too. In addition, artificial
ligands can be produced in the laboratory.

Structure of Synapses
Synapses are junctions between the
Figure 2.21
terminal buttons at the ends of the axonal
branches of one neuron and the membrane
of another. The most common type of
synapse is an axodendritic synapse, where
the axon of one neuron synapses with a
dendrite of another neuron (Figure 2.21, a).
If a neuron synapses with the soma of
another neuron it is called an axosomatic
synapse (Figure 2.21, b), and if it synapses
with the axon of another cell it is an
axoaxonic synapse (Figure 2.21, c). Let’s
examine a representative synapse in more
detail. The presynaptic membrane, located
at the end of the terminal button, faces the
postsynaptic membrane, located on the
neuron that receives the message. These
two membranes face each other across the
synaptic cleft, a gap that varies in size from
synapse to synapse but is usually around 20
nm wide. (A nanometer, nm, is one billionth
of a meter.) The synaptic cleft contains extracellular fluid, through which the neurotransmitter diffuses. A meshwork of filaments
crosses the synaptic cleft and keeps the presynaptic and postsynaptic membranes in alignment. As you can see in Figure 2.22, two
prominent structures are located in the cytoplasm of the terminal button: mitochondria and synaptic vesicles. We also see
microtubules, which are responsible for transporting material between the soma and terminal button. The presence of mitochondria
implies that the terminal button needs energy to perform its functions. Synaptic vesicles are small, rounded objects in the shape of
spheres or ovoids. (The term vesicle means “little bladder.”) A given terminal button can contain from a few hundred to nearly a million
synaptic vesicles. (See Figure 2.22.) Many terminal buttons contain two types of synaptic vesicles: large and small. Small synaptic
vesicles (found in all terminal buttons) contain molecules of the neurotransmitter. They range in number from a few dozen to several
hundred. The membrane of small
synaptic vesicles consists of
approximately 10,000 lipid
molecules into which are inserted
about 200 protein molecules.
Transport proteins fill vesicles with
the neurotransmitter, and
trafficking proteins are involved in
the release of neurotransmitters
and recycling of the vesicles.
Synaptic vesicles are found in
greatest numbers around the part
of the presynaptic membrane that
faces the synaptic cleft—near the
release zone, the region from
which the neurotransmitter is
released. In many terminal
buttons we see a scattering of

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large, dense-core synaptic vesicles. These vesicles contain one of a number of different peptides, the functions of which are described
later. Small synaptic vesicles are produced in the Golgi apparatus located in the soma and are carried by fast axoplasmic transport to
the terminal button. As we will see, some are also produced from recycled material in the terminal button. Large synaptic vesicles are
produced only in the soma and are transported through the axoplasm to the terminal buttons.

Release of Neurotransmitters
When action potentials are conducted down an axon (and down all of its branches), something happens inside all of the terminal
buttons: A number of small synaptic vesicles located just inside the presynaptic membrane fuse with the membrane and then break
open, spilling their contents into the synaptic cleft. How does an action potential cause synaptic vesicles to release neurotransmitters?
The process begins when a population of synaptic vesicles becomes “docked” against the presynaptic membrane, ready to release their
neurotransmitter into the synaptic cleft. Docking is accomplished when clusters of protein molecules attach to other protein molecules
located in the presynaptic membrane (see Figure 2.24). The release zone (see Figure 2.22) of the presynaptic membrane contains
voltage-dependent calcium channels. When the membrane of the terminal button is depolarized by an arriving action potential, the
calcium channels open. Like sodium ions, calcium ions (Ca 2+) are located in highest concentration in the extracellular fluid. Thus, when
the voltage- dependent calcium
channels open, Ca2+ flows into the
cell, propelled by electrostatic
pressure and the force of diffusion.
The entry of Ca2+ is an essential
step; if neurons are placed in a
solution that contains no calcium
ions, an action potential no longer
causes the release of a
neurotransmitter. (Calcium
transporters, similar in operation
to sodium–potassium
transporters, later remove the
intracellular Ca2+.) As we will see
later, calcium ions play many
important roles in biological
processes within cells. Calcium
ions can bind with various types of
proteins, changing their
characteristics. Some of the
calcium ions that enter the
terminal button bind with the
clusters of protein molecules that
join the membrane of the synaptic
vesicles with the presynaptic
membrane. This event makes the
segments of the clusters of protein
molecules move apart, producing a fusion pore—a hole through both membranes that enables them to fuse together. The process of
fusion takes approximately 0.1 msec and is called exocytosis (look again at Figure 2.24). The reverse of this process is called
endocytosis, where little buds of membrane pinch off into the cytoplasm and become synaptic vesicles. The appropriate proteins are
inserted into the membrane of these vesicles and the vesicles are filled with molecules of the neurotransmitter, making it ready to start
the process over from the beginning should more Ca2+ enter into the cell.

Activation of Receptors
How do molecules of a neurotransmitter produce a depolarization or hyperpolarization in the postsynaptic membrane? They do so by
diffusing across the synaptic cleft and attaching to the binding sites of special protein molecules located in the postsynaptic membrane,
called postsynaptic receptors. Once binding occurs, the postsynaptic receptors open neurotransmitter-dependent ion channels,
which permit the passage of specific ions into or out of the cell. Thus, the presence of the neurotransmitter in the synaptic cleft allows
particular ions to pass through the membrane, changing the local membrane potential. Notice that neurotransmitter molecules cannot
enter into the postsynaptic cell—only ions can enter the cell through ion channels. Neurotransmitters open ion channels by at least
two different methods, direct and indirect. The direct method is simpler, so we will describe it first. Figure 2.26 illustrates a
neurotransmitter-dependent ion channel that is equipped with its own binding site. When a molecule of the appropriate
neurotransmitter attaches to it, the ion channel opens. The formal name for this combination receptor/ion channel is an ionotropic
receptor. Ionotropic receptors were first discovered in the organ that produces electrical current in Torpedo, the electric ray,where
they occur in great number. (The electric ray is a fish that generates a powerful electrical current, not some kind of Star Wars weapon.)
These receptors, which are sensitive to a neurotransmitter called acetylcholine, contain sodium channels. When these channels are

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open, sodium ions enter the cell and depolarize the membrane. The indirect method
is more complicated. Ligand binding to some receptors does not open ion channels
directly but instead starts a chain of chemical events. These receptors are called
metabotropic receptors because they involve steps that require that the cell expend
metabolic energy. Metabotropic receptors are located in close proximity to another
protein attached to the membrane—a G protein. When a molecule of the
neurotransmitter binds with a metabotropic receptor, the receptor activates a G
protein situated inside the membrane next to the receptor. When activated, the G
protein activates an enzyme that stimulates the production of a chemical called a
second messenger. (The neurotransmitter is the first messenger.) Molecules of the
second messenger travel through the cytoplasm, attach themselves to nearby ion
channels, and cause them to open. Compared with postsynaptic potentials produced
by ionotropic receptors, those produced by metabotropic receptors take longer to
begin and last longer. The original second messenger to be discovered was cyclic AMP,
a chemical that is synthesized from ATP. Since then, several other second messengers
have been discovered. Second messengers play an important role in both synaptic and
nonsynaptic communication and they can do more than open ion channels. For
example, they can travel to the nucleus or other regions of the neuron and initiate
biochemical changes that affect the functions of the cell. They can even turn specific
genes on or off, thus initiating or terminating production of particular proteins.

Postsynaptic Potentials
Local changes in the membrane potential are Figure 2.27
called graded potentials. The amount of
change in the membrane potential is
determined by the size of the stimulus that
causes it (See Figure 2.27). Using the example
of testing the temperature in a shower, slightly
warm water would only initiate a small change
in a thermoreceptor, whereas hot water would
cause a large amount of change in the
membrane potential. In the postsynaptic cell,
graded potentials can be either depolarizing
(excitatory) or hyperpolarizing (inhibitory).
What determines the nature of the
postsynaptic potential at a particular synapse
is not the neurotransmitter itself. Instead, it is
determined by the characteristics of the
postsynaptic receptors—more specifically, by
the particular type of ion channel they open.
There are four major types of neurotransmitter-dependent ion channels found in the postsynaptic membrane: sodium, potassium,
chloride, and calcium (see Figure 2.28). Although the figure depicts only directly activated (ionotropic) ion channels, you should know
that many ion channels are activated indirectly, by metabotropic receptors coupled to G proteins. The neurotransmitter-dependent
sodium channel is the most important
source of excitatory postsynaptic
potentials. As we saw, sodium–
potassium transporters keep sodium
outside the cell, waiting for the forces
of diffusion and electrostatic pressure
to push it in. When sodium channels
are opened, the result is a
depolarization—an excitatory
postsynaptic potential (EPSP) (see
Figure 2.28a). We also saw that
sodium–potassium transporters
maintain a small surplus of potassium
ions inside the cell. If potassium
channels open, some of these cations
will follow this gradient and leave the
cell. Because K+ is positively charged,

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its efflux will hyperpolarize the membrane, producing an inhibitory postsynaptic potential (IPSP) (see Figure 2.28b). At many
synapses, inhibitory neurotransmitters open the chloride channels, instead of (or in addition to) potassium channels. The effect of
opening chloride channels depends on the membrane potential of the neuron. If the membrane is at the resting potential, nothing
happens, because (as we saw earlier) the forces of diffusion and electrostatic pressure balance perfectly for the chloride ion. However,
if the membrane potential has already been depolarized by the activity of excitatory synapses located nearby, then the opening of
chloride channels will permit Cl– to enter the cell. The influx of anions (negatively charged ions) will bring the membrane potential
back to its normal resting condition. Thus, the opening of chloride channels serves to neutralize EPSPs (see Figure 2.28c). The fourth
type of neurotransmitter-dependent ion channel is the calcium channel. Calcium ions (Ca 2+), being positively charged and being located
in highest concentration outside the cell, act like sodium ions; that is, the opening of calcium channels depolarizes the membrane,
producing EPSPs (see Figure 2.28d). But calcium does even more. As we saw earlier, the entry of calcium into the terminal button
triggers the migration of synaptic vesicles and the release of the neurotransmitter. In the dendrites of the postsynaptic cell, calcium
binds with and activates special enzymes. These enzymes have a variety of effects, including the production of biochemical and
structural changes in the postsynaptic neuron.

All types of graded postsynaptic potentials will

Figure 2.28.5
result in small changes of either depolarization or
hyperpolarization in the voltage of a membrane.
These changes can lead to the neuron reaching
threshold if the changes add together,
or summate. The combined effects of different
types of graded potentials are illustrated in Figure
2.28.5. If the total change in voltage in the
membrane is a positive 15 mV, meaning that the
membrane depolarizes from -70 mV to -55 mV,
then the graded potentials will result in the
membrane reaching threshold. Graded potentials
summate at a specific location at the beginning of
the axon to initiate the action potential, namely
the initial segment. For sensory neurons, which
do not have a cell body between the dendrites and
the axon, the initial segment is directly adjacent to
the dendritic endings. For all other neurons, the
axon hillock is essentially the initial segment of
the axon, and it is where summation takes place.
Postsynaptic Potential Summation. The result of summation of postsynaptic potentials is the
overall change in the membrane potential. At point A, several different excitatory postsynaptic These locations have a high density of voltage-
potentials add up to a large depolarization. At point B, a mix of excitatory and inhibitory gated Na+ channels that initiate the depolarizing
postsynaptic potentials result in a different end result for the membrane potential. phase of the action potential. Summation can be
spatial or temporal, meaning it can be the result
of multiple graded postsynaptic potentials at different locations on the neuron, or all at the same place but separated in time. Spatial
summation is related to associating the activity of multiple inputs to a neuron with each other. Temporal summation is the
relationship of multiple action potentials from a single cell resulting in a significant change in the membrane potential. Spatial and
temporal summation can act together, as well.

Termination of Postsynaptic Potentials

Postsynaptic potentials are brief depolarizations or
hyperpolarizations caused by the activation of postsynaptic
receptors with molecules of a neurotransmitter. They are kept
brief by two mechanisms: reuptake and enzymatic
deactivation.

Reuptake: The postsynaptic potentials produced by most

neurotransmitters are terminated by reuptake. This process
is simply an extremely rapid removal of neurotransmitter from
the synaptic cleft by the terminal button. The neurotransmitter
does not return in the vesicles that get pinched off the
membrane of the terminal button. Instead, the membrane
contains special transporter molecules that draw on the cell’s
energy reserves to force molecules of the neurotransmitter
from the synaptic cleft directly into the cytoplasm—just as
sodium–potassium transporters move Na+ and K+ across the
membrane. When an action potential arrives, the terminal
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button releases a small amount of neurotransmitter into the synaptic cleft and then takes it back, giving the postsynaptic receptors
only a brief exposure to the neurotransmitter. (See Figure 2.29.)

Enzymatic Deactivation: Enzymatic deactivation is accomplished by an enzyme that destroys molecules of the neurotransmitter.
Postsynaptic potentials are terminated in this way for acetylcholine (ACh) and for neurotransmitters that consist of peptide
molecules. Transmission at synapses on muscle fibers and at some synapses between neurons in the CNS is mediated by ACh.
Postsynaptic potentials produced by ACh are short lived because the postsynaptic membrane at these synapses contains an enzyme
called acetylcholinesterase (AChE). AChE destroys ACh by breaking it into its constituents: choline and acetate. Because neither of
these substances is capable of activating postsynaptic receptors, the postsynaptic potential is terminated once the molecules of ACh
are broken apart. AChE is an extremely energetic destroyer of ACh; one molecule of AChE will break apart more than 5,000 molecules
of ACh each second.

Effects of Postsynaptic Potentials: Neural Integration

We have seen how neurons are
interconnected by means of
synapses, how action potentials
trigger the release of
neurotransmitters, and how these
chemicals initiate excitatory or
inhibitory postsynaptic potentials.
Excitatory postsynaptic potentials
increase the likelihood that the
postsynaptic neuron will fire;
inhibitory postsynaptic potentials
decrease this likelihood.
(Remember, “firing” refers to the
occurrence of an action potential.)
Thus, the rate at which an axon fires
is determined by the relative activity
of the excitatory and inhibitory
synapses on the soma and dendrites
of that cell. If there are no active
excitatory synapses or if the activity
of inhibitory synapses is particularly
high, that rate could be close to zero.
Let’s look at the elements of this process. The interaction of the effects of excitatory and inhibitory synapses on a particular neuron is
called neural integration. The rate at which a neuron fires is controlled by the relative activity of the excitatory and inhibitory synapses
on its dendrites and soma. If the activity of excitatory synapses goes up, the rate of firing will go up. If the activity of inhibitory synapses
goes up, the rate of firing will go down. Figure 2.30 illustrates the effects of excitatory and inhibitory synapses on a postsynaptic neuron.
The top panel shows what happens when several excitatory synapses become active. The release of a neurotransmitter produces
depolarizing EPSPs in the dendrites of the neuron. These EPSPs (represented in red) are then transmitted down the dendrites, across
the soma, to the axon hillock located at the base of the axon. If the depolarization is still strong enough when it reaches this point, the
axon will fire (see Figure 2.30a). Let’s consider what would happen if, at the same time, inhibitory synapses also become active.
Inhibitory postsynaptic potentials are hyperpolarizing—they bring the membrane potential away from the threshold of excitation.
Thus, they tend to cancel the effects of excitatory postsynaptic potentials. Note that neural inhibition (that is, an inhibitory postsynaptic
potential) does not always produce behavioral inhibition. For example, suppose a group of neurons inhibits a particular movement. If
these neurons are inhibited, they will no longer suppress the behavior. Thus, inhibition of the inhibitory neurons makes the behavior
more likely to occur. Of course, the same is true for neural excitation. Excitation of neurons that inhibit a behavior suppresses that
behavior. For example, when we are dreaming, a particular set of inhibitory neurons in the brain becomes active and prevents us from
getting up and acting out our dreams. Neurons are elements in complex circuits; without knowing the details of these circuits, one
cannot predict the effects of the excitation or inhibition of one set of neurons on an organism’s behavior.

Other Types of Synapses

So far, the discussion of synaptic activity has referred only to the effects of postsynaptic excitation or inhibition. These effects occur
when terminal synapses occur on postsynaptic dendrites or somas. Synapses can also occur on axons. These synapses work differently.

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Axoaxonic synapses do not contribute directly to neural integration. Instead, they alter the
amount of neurotransmitter released by the terminal buttons of the postsynaptic axon.
They can produce presynaptic modulation: presynaptic inhibition or presynaptic
facilitation. (See Figure 2.31.) As you know, the release of a neurotransmitter by a terminal
button is initiated by an action potential. Normally, a particular terminal button releases a
fixed amount of neurotransmitter each time an action potential arrives. However, the
release of a neurotransmitter can be modulated by the activity of axoaxonic synapses. If the
activity of the axoaxonic synapse decreases the release of the neurotransmitter, the effect
is called presynaptic inhibition. If it increases the release, it is called presynaptic
facilitation. Many very small neurons have extremely short processes and apparently lack
axons. These neurons form dendrodendritic synapses, or synapses between dendrites.
Because these neurons lack long axonal processes, they do not transmit information from
place to place within the brain. Most investigators believe that they perform regulatory
functions, perhaps helping to organize the activity of groups of neurons. Because these
neurons are so small, they are difficult to study; therefore, little is known about their
function. Some larger neurons also form dendrodendritic synapses. Some of these synapses
are chemical, indicated by the presence of synaptic vesicles in one of the juxtaposed
dendrites and a postsynaptic thickening in the membrane of the other. Other synapses are
electrical; the membranes meet and almost touch, forming a gap junction. The membranes on both sides of a gap junction contain
channels that permit ions to diffuse from one cell to another. Thus, changes in the membrane potential of one neuron induce changes
in the membrane of the other. Although most gap junctions in vertebrate synapses are dendrodendritic, gap junctions at postsynaptic
dendrites and somas can also occur. Gap junctions are common in invertebrates; their function in the vertebrate nervous system is not
known.

Agonists vs Antagonists
There are many ways that a drug can
alter how a synapse functions.
However, we can group all the
effects into whether the drug
increases the effect of the
neurotransmitter at the synapse or
decreases it. If the drug increases the
effect of the neurotransmitter it is
called an agonist. If it decreases the
effect of the neurotransmitter it is
called an antagonist. So, if a
neurotransmitter is inhibitory, an
agonist will increase the inhibitory
effect of the neurotransmitter,
whereas an antagonist will decrease
the inhibitory effect. If the
neurotransmitter is excitatory, an
agonist will increase the excitatory
effect, and an antagonist will
decrease the excitatory effect.
Figure 4.7 outlines a number of
different ways agonists and
antagonists can influence neuronal
communication (agonist effects are
in purple and antagonist effects are
in pink).

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Neurotransmitters and Neuromodulators

There are many different kinds of neurotransmitters— several dozen at least. In the brain, most synaptic communication is
accomplished by two amino acid neurotransmitters: one with excitatory effects (glutamate) and one with inhibitory effects
(gammaaminobutyric acid, or GABA). A secondary inhibitory amino acid neurotransmitter, glycine, is found in the spinal cord and
lower brain stem. Most of the activity of local circuits of neurons involves balances between the excitatory and inhibitory effects of
these chemicals, which are responsible for most of the information transmitted from place to place within the brain. In fact, there are
probably no neurons in the brain that do not receive excitatory input from glutamate-secreting terminal buttons and inhibitory input
from neurons that secrete either GABA or glycine. With the exception of neurons that detect painful stimuli, which secrete a different
peptide, all sensory organs transmit information to the brain through axons whose terminals release glutamate. While GABA and
glutamate are released by cells located throughout the brain, most other neurotransmitter systems include cells organized into specific
pathways with cell bodies originating in one (or more) brain regions projecting to one (or more) other brain regions. What do all the
other neurotransmitters do? In general, they have modulating effects rather than information transmitting effects. That is, the release
of neurotransmitters other than glutamate, GABA, and glycine tends to activate or inhibit entire circuits of neurons that are involved
in particular brain functions related to behavior and mental processes. Because particular drugs can selectively affect neurons that
secrete particular neurotransmitters, they can have specific effects on behavior.

Neurotransmitters fall into a number of general categories, which include: Table 4

 Amino acids (glutamate, GABA, glycine, aspartate)
 Biogenic amines (acetylcholine)
 Indoleamines (serotonin)
 Catecholamines (dopamine, norepinephrine, epinephrine)
 Peptides (endorphins, substance P)
 Gases (nitric oxide, which is often released by neurons when
stimulated, which causes nearby blood vessels to dilate, thereby
increasing blood flow to that area – important concept for fMRI. Not
to be confused with nitrous oxide, better known as laughing gas).

The general effect of many of these neurotransmitters can be seen in Table 4.

Note that some can have both excitatory and inhibitory effects – it all depends
on what type of channel it opens and these can be different for different system.
For a general overview of the various roles different neurotransmitters play in nervous system functions, see Table 4.1 below.

Adapted from:
Carlson, N.R. & Birkett, M.A. (2017) Physiology of Behavior, (12 th ed.) Boston: Pearson.
Anatomy and Physiology online textbook: https://opentextbc.ca/anatomyandphysiology/
Biology Online Dictionary: https://www.biology-online.org/dictionary/Decremental_conduction

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