Ganong's Review of Medical Physiology, 23rd Edition

Postsynaptic
density
Presynaptic
cell
Postsynaptic
cell
Dendrite
Soma
Axon
Microtubules
Mitochondria
Clear vesicles
Active zone
Dendritic spine
Axodendritic
Axodendritic
Axosomatic
Axo-axonal
FIGURE 6–3 Axodendritic, axoaxonal, and axosomatic
synapses. Many presynaptic neurons terminate on dendritic spines,
as shown at the top, but some also end directly on the shafts of dendrites.
Note the presence of clear and granulated synaptic vesicles in
endings and clustering of clear vesicles at active zones.
neuropeptides. The vesicles and the proteins contained in their
walls are synthesized in the neuronal cell body and transported
along the axon to the endings by fast axoplasmic transport. The
neuropeptides in the large dense-core vesicles must also be produced
by the protein-synthesizing machinery in the cell body.
However, the small clear vesicles and the small dense-core vesicles
recycle in the nerve ending. These vesicles fuse with the cell
membrane and release transmitters through exocytosis and are
then recovered by endocytosis to be refilled locally. In some
instances, they enter endosomes and are budded off the endosome
and refilled, starting the cycle over again. The steps
involved are shown in Figure 6–4. More commonly, however,
the synaptic vesicle discharges its contents through a small hole
CHAPTER 6 Synaptic & Junctional Transmission 117
in the cell membrane, then the opening reseals rapidly and the
main vesicle stays inside the cell (kiss-and-run discharge). In this
way, the full endocytotic process is short-circuited.
The large dense-core vesicles are located throughout the presynaptic
terminals that contain them and release their neuropeptide
contents by exocytosis from all parts of the terminal.
On the other hand, the small vesicles are located near the synaptic
cleft and fuse to the membrane, discharging their contents
very rapidly into the cleft at areas of membrane thickening
called active zones (Figure 6–3). The active zones contain
many proteins and rows of calcium channels.
The Ca 2+ that triggers exocytosis of transmitters enters the presynaptic
neurons, and transmitter release starts within 200 μs.
Therefore, it is not surprising that the voltage-gated Ca 2+ channels
are very close to the release sites at the active zones. In addition,
for the transmitter to be effective on the postsynaptic neuron
requires proximity of release to the postsynaptic receptors. This
orderly organization of the synapse depends in part on neurexins,
proteins bound to the membrane of the presynaptic neuron that
bind neurexin receptors in the membrane of the postsynaptic
neuron. In many vertebrates, neurexins are produced by a single
gene that codes for the α isoform. However, in mice and humans
they are encoded by three genes, and both α and β isoforms are
produced. Each of the genes has two regulatory regions and
extensive alternative splicing of their mRNAs. In this way, over
1000 different neurexins are produced. This raises the possibility
that the neurexins not only hold synapses together, but also provide
a mechanism for the production of synaptic specificity.
As noted in Chapter 2, vesicle budding, fusion, and discharge
of contents with subsequent retrieval of vesicle membrane
are fundamental processes occurring in most, if not all,
cells. Thus, neurotransmitter secretion at synapses and the
accompanying membrane retrieval are specialized forms of the
general processes of exocytosis and endocytosis. The details of
the processes by which synaptic vesicles fuse with the cell
membrane are still being worked out. They involve the v-snare
protein synaptobrevin in the vesicle membrane locking with
the t-snare protein syntaxin in the cell membrane; a multiprotein
complex regulated by small GTPases such as rab3 is also
involved in the process (Figure 6–5). The synapse begins in the
presynaptic and not in the postsynaptic cell. The one-way gate
at the synapses is necessary for orderly neural function.
Clinical Box 6–1 describes the how neurotoxins can disrupt
transmitter release in either the CNS or at the neuromuscular
junction.
ELECTRICAL EVENTS IN
POSTSYNAPTIC NEURONS
EXCITATORY & INHIBITORY
POSTSYNAPTIC POTENTIALS
Penetration of an α-motor neuron is a good example of the
techniques used to study postsynaptic electrical activity. It is