Neuronal Signaling and the Structure of the Nervous System
169
Presynaptic cell
Postsynaptic cell
2
1
High-frequency
action potentials
in presynaptic
cell
Secretory vesicle
containing glutamate
Glutamate
is released
3
Glutamate
binds to
both channels
4
Na
+
entry
depolarizes
cell by
20–30mV
5
Depolarization
drives Mg
2
+
ion out of pore
6
Ca
2
+
entry activates
second messenger
systems
7
Long-lasting increase
in glutamate receptors
and sensitivity
8
Long-lasting increase
in glutamate synthesis
and release
AMPA
receptor
NMDA
receptor
Na
+
Ca
2
+
Mg
2
+
Retrograde
messenger
+
+
+
+
+
+
Figure 6–36
Long-term potentiation at glutamatergic synapses. Episodes of intense fi ring across a synapse result in structural and chemical changes that
amplify the strength of synaptic signaling during subsequent activation. See text for description of each step. Note that both AMPA and
NMDA receptors are nonspecifi c cation channels, but the main current through AMPA channels is sodium whereas NMDA channels allow
signifi cant calcium current.
with widespread actions—can cause unwanted side effects.
The drug lysergic acid diethylamide (
LSD
) is thought to block
serotonin receptors in the brain, thereby preventing normal
serotonergic neurotransmission. However, it is not clear how
this action produces the intense visual hallucinations that are
produced by ingestion of this drug.
Serotonin is also present in many nonneural cells (e.g.,
blood platelets and certain cells of the immune system and
digestive tract). In fact, the brain contains only 1 to 2 percent
of the body’s serotonin.
Amino Acid Neurotransmitters
In addition to the neurotransmitters that are synthesized from
amino acids, several amino acids themselves function as neu-
rotransmitters. Although the amino acid neurotransmitters
chemically fi t the category of biogenic amines, neurophysiolo-
gists traditionally put them into a category of their own. The
amino acid neurotransmitters are by far the most prevalent
neurotransmitters in the central nervous system, and they
affect virtually all neurons there.
Glutamate
There are a number of
excitatory amino acids, aspartate
being one example, but the most common neurotransmitter at
excitatory synapses in the CNS is the amino acid
glutamate.
As
with other neurotransmitter systems, pharmacological manipu-
lation of the receptors for glutamate has permitted identifi cation
of specifi c receptor subtypes by their ability to bind natural and
synthetic ligands. Although metabotropic glutamate receptors
do exist, the vast majority are ionotropic, with two important
subtypes being found in postsynaptic membranes. They are
designated as
AMPA receptors
(identifi ed by their binding to
α
-amino-3 hydroxy-5 methyl-4 isoxazole proprionic acid) and
NMDA receptors
(which bind
N
-methyl-
D
-aspartate).
Cooperative activity of AMPA and NMDA receptors has
been implicated in a phenomenon called
long-term potentia-
tion (LTP).
This mechanism couples frequent activity across a
synapse with lasting changes in the strength of signaling across
that synapse, and is thus thought to be a cellular process under-
lying learning and memory.
Figure 6–36
outlines the mecha-
nism in stepwise fashion. When a presynaptic neuron fi res action
potentials (step 1), glutamate is released from presynaptic ter-
minals (step 2) and binds to both AMPA and NMDA receptors
on postsynaptic membranes (step 3). AMPA receptors function
just like the excitatory postsynaptic receptors discussed earlier—
when glutamate binds, the channel becomes permeable to both
sodium and potassium, but the larger entry of sodium creates
a depolarizing EPSP of the postsynaptic cell (step 4). By con-
trast, NMDA-receptor channels also mediate a substantial cal-
cium fl ux, but opening them requires more than just glutamate
binding. A magnesium ion blocks NMDA channels when the
membrane voltage is near the negative resting potential, and to
previous page 197 Vander's Human Physiology The Mechanisms of Body Function read online next page 199 Vander's Human Physiology The Mechanisms of Body Function read online Home Toggle text on/off