This project aims to investigate the roles played by synapse elimination during the development of neuromuscular connections. Three aspects of this regressive process will be studied. The roles played by the coupling of developing muscle cells by gap junctions in the regulation of synapse elimination will be examined by analysis of the patterns of dye coupling of physiologically identified and injected cells. In particular, the types of coupling present and their relationship to the innervation of secondary myotubes will be investigated. The interaction of different elements of the neuronal cytoskeleton in the selective stabilization of neuromuscular synapses during the period of synapse elimination will be studied using immunohistochemical techniques. The appearance, interaction, and post-translational modification of different elements will be correlated with the attainment of the adult pattern of innervation. Finally, it will be determined whether synapse elimination in the very early postnatal period functions to refine the patterns of neuromuscular connectivity. Analysis of innervation patterns in animals in which synapse elimination has been prolonged by neonatal tenotomy will be used to determine whether synapse elimination actively corrects errors of neuromuscular connectivity. Synapse elimination is a common feature in the development of the nervous system, yet little is known about its functional role. By examination of two aspects of its cellular regulation and one function which it might perform, it is anticipated that new insights into the functional roles of this widespread regressive process will b$ made which will be applicable to many different areas of neuronal development. It is hoped that the results of these studies will also have general applicability to elucidating mechanisms of developmental disorders of the nervous system.
