FORMATION AND ELIMINATION OF NERVE MUSCLE SYNAPSES

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The leg neuromuscular system of the cockroach is one in which the formation of connections between identified motor neurons and muscles may be examined in the adult during axonal regeneration and in the embryo during development. We have demonstrated that during regeneration the coxal depressor muscles are initially randomly innervated by all axotomized neurons. This is similar to what occurs during regeneration in mammals. However, in the cockroach, at later times of regeneration the inappropriate connections are eliminated or the correct ones are maintained until one is left with the original innervation pattern. This is similar to events taking place during embryonic development in mammals. Using anatomical and electrophysiological techniques and surgical manipulations we propose to determine the cellular mechanisms involved in the selective elimination of inappropriate connections. Using various biochemical approaches, including hybridoma technology, we propose to identify, isolate, characterize and demonstrate a function for those macromolecules responsible for generating the specificity of these cellular interactions. In addition, using immunohistochemical techniques, attemps will be made to determine whether the same macromolecules and cellular interactions are involved in the initial formation of the innervation pattern of the muscles during embryonic development. The knowledge acquired in this investigation will help us to attain a better understanding of the more general biological phenomena of intercellular recognition and cell growth. Metastasis of tumors, infection of cells by viruses, bacteria and parasites all involve a specific recognition process. Knowledge of the role of cell surface macromolecules in these processes will lead to better therapeutic treatments. The information acquired on the mechanism of the successful regeneration of cockroach motor neuron may also be applicable to attempts to increase the probability of obtaining successful functional regeneration of neurons after injury in humans. Such knowledge would be helpful for the treatment of paraplegics and for other neurological disorders involving neuronal injury like strokes, multiple sclerosis or head injury.