SYNAPTIC SPECIFICITY IN THE SPINAL CORD

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Our goal is the identification of the nerve terminal membrane components involved in mediating specific synaptic linkages in the spinal cord. Constituents of the nerve terminal surface plasma membrane are widely believed to have a crucial role in the formation and maintenance of synaptic connections. Presumably, the specific synaptic relationships formed by different populations of spinal afferent nerve terminals are reflected by differences in the composition of their presynaptic membranes. However, the unique presynaptic membrane proteins involved in mediating specific synaptic linkages are yet to be identified. Monoclonal antibodies directed against synaptic membrane antigens have been developed which identify presynaptic membrane proteins associated with spinal nerve terminals. While many of these antibodies recognize ubiquitous components of synaptic endings, others are specific to subpopulations of spinal afferent nerve terminals. One in particular is directed against a synaptic vesicle membrane antigen which appears to have some of the properties expected of a presynaptic membrane protein involved in mediating specific synaptic linkages. The aims of the proposed studies are to: 1) determine to what extent this antigen is associated with the nerve terminal plasma membrane and specifically with the synaptic junctional region and synaptic cleft; 2) characterize the antigen and determine whether it is a peripheral or integral membrane protein; 3) purify the antigen and develope a monospecific, polyclonal antiserum to it; 4) identify the origins and connections of the spinal afferent neurons containing the antigen and determine the putative neurotransmitter(s) in these cells; and 5) map the distribution of the antigen in the brain, peripheral nervous system and in non-neuronal secretory cells and determine the time course of expression of the antigen in the spinal cord during development. A second part of the studies will be directed at identifying other nerve terminal synaptic plasma membrane proteins which may be involved in mediating synaptic specificity in the spinal cord. Immunocytochemical methods for light and electron microscopy, along with various immunochemical procedures will be used in these investigations. The results of these studies are likely to have significant implications for understanding the mechanisms involved in the formation and maintenance of synaptic connections in the spinal cord.