The vertebrate synapse is a specialized form of cell-cell contact critical in nervous system function. The plasma membrane and underlying associated cytoplasmic proteins of both the pre- and postsynaptic sides of the synapse form a highly specialized, ultrastructurally unique complex that is the intracellular location of many biochemically and physiologically regulated synaptic events. The proposed study is designed to examine the molecular organization of nervous system presynaptic terminals. This will be accomplished by the powerful combination of well-documented technologies: labelling of the presynaptic, subcellular cytoplasmic compartments within the terminal by axonal transport, b) the enrichment of radiolabeled presynaptic terminals by careful and rigorous preparation of synaptosomes, and c) the subjection of the radiolabeled synaptosomes to biochemical experiments that are designed to test the functional role of the radiolabeled proteins within the terminals. Information we may thus obtain through basic research on normal biochemistry, molecular organization, and functioning of the synapse will aid a) in understanding the way the presynaptic terminal performs its important biological tasks under the stress of disease states, and b) in discerning the origins and source of malfunctions that affect the synapse directly.
