SYNAPTIC SPECIFITY IN THE SPINAL CORD

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The long term goal of these studies 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 the time course of expression of this antigen in the spinal cord during development including, ultrastructural localization of the antigen during synaptogenesis in the spinal dorsal horn; 2) identify the origins of the spinal neuronal pathways which contain the antigen and determine the putative neuro-transmitter(s) in these neurons; 3) map the distribution of the antigen in other parts of the central and peripheral nervous system and in non-neuronal secretory cells; 4) determine to what extent this antigen is associated with the nerve terminal plasma membrane and specifically with the synaptic junctional region and synaptic cleft; 5) characterize the antigen the determine whether it is a peripheral or integral membrane protein 6) purify the antigen and develop a monospecific, polyclonal antiserum to it. 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 an 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.