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.

Figure 19.1

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 correct locations.

Figure 19.2

Proof that the basal lamina contains the instructions for formation of both pre- and post-synaptic differentiation.

Figure 19.3

"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.

Figure 19.4

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.

Figure 19.6

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).

Figure 19.9

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.

Figure 19.10

The process of losing a terminal - both pre- and post-synaptic components are lost. This is a result of nerve crush in adult animals.

Now onto the visual system in the cortex

Figure 19.13

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.

Figure 19.14

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.

Figure 19.15

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.

Figure 19.16

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.

Figure 19.17

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 connections.

Figure 19.18

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.