Chemical synaptic transmission in the nervous system occurs at highly specialized junctions between pre- and postsynaptic cells. Although much is known about the ultrastructure of chemical synapses and about the electrophysiological events that occur during transmission, little is known at a molecular level about the specialized structures that occur at synapses and how they are assembled. The objective of the experiments described in this proposal is to understand synaptic development and function at a chemical and cellular level. We propose to identify molecules that form part of specialized structures at synapses, to investigate their function and to use them to study the cellular interactions involved in assembly of these structures during development. Our experiments will be carried out on both nerve-muscle and nerve-nerve synapses in vivo and in organ culture systems. Although we will use a number of techniques in these investigations, the proposal focuses on the use of antibodies as a major tool in identifying and studying specific synaptic components. To provide a general background for the overall proposal, the following discussion seeks to highlight important questions and areas of common interest. It focuses on the neuromuscular junction with references, where appropriate, to other synapses. A more detailed treatment of individual topics is given with each of the six projects.
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