STRUCTURE AND FUNCTION OF REGENERATING SYNAPSES

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If a skeletal muscle and/or its motor nerve is damaged, neuromuscular function ceases. With time, muscle fibers regenerate, the portions of the axons that remain connected to the central nervous system grow to them, and neuromuscular function is restored. Recovery of function, however, is seldom complete. A pianist who severs a nerve to muscles of the hand can regain use of the hand for moving objects but will never perform again. Studies on specific aspects of regeneration in situations where they can be examined in detail are requisite for devising ways to enhance functional recovery in the neuromuscular system after damage resulting from disease or trauma. The long-range objectives of this project are to identify structures in nerve and muscle that influence regeneration of the neuromuscular junction and to determine what sorts of information they provide. The specific aims of the experiments outlined in this project are to: a) characterize the influence of Schwann cells and their basal lamina sheaths on the direction of growth of regenerating axons; b) to examine the influence of tissue components other than myofibers on the differentiation and maintenance of regenerating axon terminals; c) to characterize the role of tissue components other than axon terminals on the development of the postsynaptic apparatus in regenerating myofibers; and d) to identify and characterize specific molecules involved in regeneration of the neuromuscular junction. These experiments will be conducted under in vivo and in vivo situations. They will involve a variety of surgical, light and electron microscopical, biochemical, immunochemical and cell biological techniques. The vertebrates involved in the experiments will be frogs, rats, mice and Torpedo Californica.