C h a p t e r 3 4
Organization and Control of Neural Function
827
These vesicles protect the neurotransmitters from enzyme
destruction in the nerve terminal. There may be thousands
of vesicles in a single terminal, each containing 10,000 to
100,000 transmitter molecules. Membrane depolarization
due to arrival of an action potential causes the vesicles to
move to the cell membrane and release their neurotrans-
mitter molecules by fusion of the vesicular membrane with
the outer cell membrane.
Once a neurotransmitter has exerted its effects on
the postsynaptic membrane, its rapid removal is neces-
sary to maintain precise control of neural transmission.
A released transmitter can : (1) be broken down into
inactive substances by enzymes, (2) be taken back up into
the presynaptic neuron in a process called
reuptake
, or
(3) diffuse away into the intercellular fluid until its con-
centration is too low to influence postsynaptic excitabil-
ity. For example, acetylcholine is rapidly broken down
by acetylcholinesterase into acetic acid and choline, with
the choline being taken back into the presynaptic neuron
for reuse in acetylcholine synthesis. The catecholamines
are largely taken back into the neuron in an unchanged
form for reuse. Catecholamines also can be degraded by
enzymes, such as catechol-
O
-methyltransferase (COMT)
in the synaptic space or monoamine oxidase (MAO)
in the nerve terminals. Catechol-
O
-methyltransferase
inhibitors and MAO inhibitors are used in the treat-
ments of various conditions, such as Parkinson dis-
ease, major depression, and anxiety (see the Autonomic
Neurotransmission section for detail).
Postsynaptic Potentials
A neuron’s cell body and dendrites are covered by thou-
sands of synapses, any or many of which can be active at
any moment. Because of the interaction of this rich synap-
tic input, each neuron resembles a little computer, in which
circuits of many neurons interact with one another. It is
the complexity of these interactions and the subtle inte-
grations involved in excitatory and inhibitory responses
that give rise to the nervous system’s intelligence.
Neurotransmitters exert their actions through specific
proteins, called
receptors
, embedded in the postsynap-
tic membrane. These receptors are tailored precisely to
match the size and shape of the transmitter. In each case,
the interaction between a neurotransmitter and recep-
tor causes the opening or closing of ion channels in the
postsynaptic membrane, resulting in a transient, local
change in the polarization of the postsynaptic mem-
brane, called a
postsynaptic potential
. There are two
types of postsynaptic potentials: excitatory and inhibi-
tory. If opening of the ion channel results in a net gain
of positive charge across the membrane, causing the
potential to move close to zero, the membrane is said to
be
depolarized
. This is called an
excitatory postsynaptic
potential
, since it brings the resting potential closer to its
firing threshold. If, on the other hand, opening of the ion
channel results in a net gain of negative charge causing
the potential to move further from zero, the membrane
is said to be
hyperpolarized
. This is called an
inhibitory
postsynaptic potential
, since it causes the resting mem-
brane potential to move further from threshold.
Chemical SynapticTransmission
The function of the nervous system relies on chemical
substances that serve as synaptic messengers. These mes-
sengers include neurotransmitters, neuromodulators,
and neurotrophic or nerve growth factors.
Neurotransmitters.
Neurotransmitters are endogenous
chemicals that facilitate the transmission of signals from
one neuron to the next across synapses. There are many
different ways to classify neurotransmitters, including by
whether they produce excitatory or inhibitory effects on
postsynaptic membranes and by their chemical structure.
A neurotransmitter is classified as
excitatory
if it
activates a receptor; for example, glutamate, the most
common excitatory neurotransmitter in the brain,
increases the probability that the target cell will fire
an action potential. A neurotransmitter is classified as
inhibitory
if it inhibits a receptor; gamma aminobutyric
acid (GABA) is the brain’s main inhibitory neurotrans-
mitter. There are, however, other neurotransmitters for
which both excitatory and inhibitory receptors exist; for
example, acetylcholine is excitatory when it binds to a
receptor at a myoneural junction, and it is inhibitory
when it binds to a receptor at the sinoatrial node in the
heart. Finally, some types of receptors activate complex
metabolic pathways in the postsynaptic cell to produce
effects that cannot appropriately be called either excit-
atory or inhibitory. Receptors are named according to
the type of neurotransmitter with which they interact.
For example, a
cholinergic receptor
is a receptor that
binds acetylcholine.
In addition to function, neurotransmitters can be
broadly categorized into three groups according to their
chemical structure: (1) amino acids, (2) peptides, and (3)
monoamines. Amino acids, such as glutamine, glycine,
and GABA, serve as neurotransmitters at most CNS
synapses. GABA mediates most synaptic inhibition in
the CNS. Drugs such as the benzodiazepines (e.g., the
tranquilizer diazepam) and the barbiturates exert their
action by binding to their own distinct receptor on a
GABA-operated ion channel. The drugs by themselves
do not open the channel, but they change the effect that
GABA has when it binds to the channel at the same time
as the drug.
Peptides
are low–molecular-weight mol-
ecules that are made up of two or more amino acids.
Neuropeptides are peptides used by neurons to com-
municate with each other. They include somatostatin,
substance P, and opioid peptides such as endorphins and
enkephalins, which are involved in pain sensation and
perception (see Chapter 35). A
monoamine
is an amine
molecule containing one amino group (−NH
2
group).
All monoamines are derived from aromatic amino acids
like phenylalanine, tyrosine, and tryptophan. Serotonin,
dopamine, norepinephrine, and epinephrine are exam-
ples in this category.
Neuromodulators.
Another class of messenger mole-
cules, known as
neuromodulators
, also may be released
from axon terminals. In contrast to neurotransmitters,
neuromodulators do not directly activate ion-channel
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