55: Formation and Elimination of Synapses

Introduction

• Recognition of Synaptic Targets Is Specific

  • Recognition Molecules Promote Selective Synapse Formation

  • Different Synaptic Inputs Are Directed to Discrete Domains of the Postsynaptic Cell

  • Neural Activity Sharpens Synaptic Specificity

• Principles of Synaptic Differentiation Are Revealed at the Neuromuscular Junction

  • Differentiation of Motor Nerve Terminals Is Organized by Muscle Fibers

  • Differentiation of the Postsynaptic Muscle Membrane Is Organized by the Motor Nerve

  • The Nerve Regulates Transcription of Acetylcholine Receptor Genes

  • The Neuromuscular Junction Matures in a Series of Steps

• Central Synapses Develop in Ways Similar to Neuromuscular Junctions

  • Neurotransmitter Receptors Become Localized at Central Synapses

  • Synaptic Organizing Molecules Pattern Central Nerve Terminals

  • Glial Cells Promote Synapse Formation

• Some Synapses Are Eliminated After Birth

• An Overall View

So far we have examined three stages in the development of the mammalian nervous system: the formation and patterning of the neural tube, the birth and differentiation of neurons and glial cells, 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. Usually synapses must be formed at specific sites on the postsynaptic cell; some axons form synapses on dendrites, others on cell bodies, and yet others on axons or nerve terminals. Cellular and subcellular specificity are evident throughout the brain, but we will illustrate the general features of synapse formation with a few well-studied classes of neurons.

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, and this simplicity has also helped in the analysis of developing synapses. In this chapter we use the neuromuscular synapse to illustrate key features of synaptic development, and we also apply insights from this peripheral synapse to examine the synapses that form in the central nervous system.

Finally, once formed, synapses continue to mature, often undergoing major rearrangements. One striking aspect of later development is the wholesale elimination of a large fraction of synapses, a process that is usually accompanied by the growth and strengthening of surviving synapses. Like neuronal cell death (see Chapter 53), synapse elimination is a puzzling and seemingly wasteful step in ...