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SO FAR, WE HAVE EXAMINED THREE STAGES in the development of the mammalian nervous system: the formation and patterning of the neural tube, the generation and differentiation of neurons and glia, and the growth and guidance of axons. One additional step must occur before the brain becomes functional: the formation of synapses. Only when synapses are formed and functional can the brain go about the business of processing information.

Three key processes drive synapse formation. First, axons make choices among many potential postsynaptic partners. By forming synaptic connections only on particular target cells, neurons assemble functional circuits that can process information. In many cases, synapses are even formed at specific sites on the postsynaptic cell; some types of axons form synapses on dendrites, others on cell bodies, and yet others on axons or nerve terminals. Although cellular and subcellular specificity are evident throughout the brain, the general features of synapse formation can be illustrated with a few well-studied examples.

Second, after cell–cell contacts have formed, the portion of the axon that contacts the target cell differentiates into a presynaptic nerve terminal, and the domain of the target cell contacted by the axon differentiates into a specialized postsynaptic apparatus. Precise coordination of pre- and postsynaptic differentiation depends on interactions between the axon and its target cell. Much of what we know about these interactions comes from studies of the neuromuscular junction, the synapse between motor neurons and skeletal muscle fibers. The simplicity of this synapse made it a favorable system to probe the structural and electrophysiological principles of chemical synapses (Chapter 12), and this simplicity has also helped in the analysis of developing synapses. We will use the neuromuscular synapse to illustrate key features of synaptic development and then apply insights from this peripheral synapse to examine synapses that form in the brain.

Finally, once formed, synapses mature, often undergoing major rearrangements. One striking aspect of the rearrangement is that as some synapses grow and strengthen, many others are eliminated. Like neuronal cell death (Chapter 46), synapse elimination at first glance is a puzzling and seemingly wasteful step in neural development. It is increasingly clear, however, that it plays a key role in refining initial patterns of connectivity. We will discuss the main features of synaptic rearrangement at the neuromuscular junction, where it has been studied intensively, as well as at synapses between neurons, where it also is prominent.

Synapse formation stands at an interesting crossroads in the sequence of events that assemble the nervous system. The initial steps in this process appear to be largely “hardwired” by molecular programs. However, as soon as synapses form, the nervous system begins to function, and the activity of neural circuits plays a critical role in subsequent development. Indeed, the information-processing capacity of the nervous system is refined through its use, most dramatically in early postnatal life but ...

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