Lecture 9: Synapse Formation and Elimination
We begin with the formation of the neuromuscular junction -- the
synapse of the motor neuron upon the muscle fiber. Remember that
the correct motor neuron must connect with the correct muscle
for adaptive movement to occur.
Structure of the normal neuromuscular junction has many specializations
that must form pre- and post-synaptically for full function to
occur. Also, the receptors and vesicles must accumulate in the
Proof that the basal lamina contains the instructions for formation
of both pre- and post-synaptic differentiation.
"Agrin" induces the redistribution of the acetylcholine
receptors, which must cluster appropriately for function to be
maximal. Motor neurons synthesize and secrete the agrin which
then causes the receptors to cluster under the terminal.
Synapse specific gene expression. It is important to know that
muscle cells are multinucleated. They are formed by many cells
fusing together and sharing their nuclei. In these huge cells,
then, the nuclei under the synapse are induced by the nerve terminal
to express different genes than do the nuclei farther away. The
extracellular signal is most likely coming from the basal lamina.
At birth muscle fibers and their terminals are innervated by multiple
nerve fibers. Over developmental time, the branches of a given
axon retract, and only one fiber innervates a given muscle fiber.
A given motor neuron will innervate multiple fibers, however.
When the nerve is cut and regenerates (remember this is the periphery!)
the process is similar. However, not shown here, the fibers will
not necessarily have the same spatial locations.
Figure 19.7 & .8
Synapse loss at the neuromuscular junction. The termnals initially
appear to be random in their distribution, and loss appears to
be a very local process. The process appears to be one of one
axon terminal expanding as the other shrinks (19.8).
The loss of the terminal by a given axon seems to be due to shriveling
of the axon and retraction of the end of the terminal.
The process of losing a terminal - both pre- and post-synaptic
components are lost. This is a result of nerve crush in adult
Now onto the visual system in the cortex
The cortical wiring is apparently a function of synapse elimination
and strengthening on the basis of activity dependent processes.
Both pre- and post-synaptic elements have to have matching activity
for the synapse to be strong and survive. Synapses that are not
fortified by correctly timed activity will be eliminated.
In the normal cortex, the two eyes have equal and alternating
representation (A). When one eye is sutured closed at birth the
open eye spreads out its axons to take over more cortical area.
This is shown by backfilling the optic nerve fibers with a compound
that crosses syanpses and tracing the fibers into the cortical
surface (B). The same kind of dominance is seen in the lateral
geniculate nucleus (a thalamic structure which receives inputs
directly from the optic nerve) (C). If TTX which blocks nerve
action potentials is injected into the cells of the thalamus prevents
the formation of the layers. Thus, the post-synaptic activity
is required as well as pre-synaptic activity.
Diagram of the process believed to underlie the accurate innervation
of the visual cortex. The process requires withdrawing of inappropriate
synapses and addition of proper synapses based on activity.
Drawings of the fibers that result from suture of one eye and
injection of TTX into the cortex. Upper row is non-deprived and
deprived eye fibers; lower row is non-injected and injected fibers
- both are left to right respectively. Thus, the deprived eye
causes fibers to shrink back. TTX on the other hand, causes fibers
to sprout and search around.
There are waves of activity across the retina. These occur periodically.
These occur even when there is no visual stimulation and are present
from birth until the eyes open. Thus the retina is generating
activity even when the eyes are still sealed. This activity is
used, therefore, for the activity dependent formation of cortical
The activity of the retina can therefore lead to the segregation
of the lateral geniculat nuclear fibers. This is a diagram of
how it could happen.