The embryological development of innervation of the skeletal muscle occurs through a series of successive steps. The first step involves the projection of motor neurons to their peripheral destination. Initially, an excess number of motor neurons project to the appropriate target muscle and subsequently about one half of the motor neurons degenerate. The specific objective of this proposal is to determine whether motor neurons compete among themselves to form synaptic connections with the muscle during the course of embryonic development of innervation. The trochlear nucleus and its sole target of innervation, the superior oblique muscle of the eye, will be used to test the """"""""competition"""""""" hypothesis. Competition among neurons will be eliminated or greatly reduced by restricting the size of neuron pool initially projecting into the target muscle. The trochlear nucleus of duck embryos will be substituted with the trochlear nucleus of quails which contains fewer motor neurons through grafting of midbrain. The peripheral and central connections of the grafted trochlear motor neurons will be monitored by HRP tracing technique, histology and electron microscopy. The functional status of afferent and efferent connections of the grafted motor neurons will be assessed by electrophysiological means. Competition will be assessed by counting the number of trochlear motor neurons that survive by virtue of making appropriate synaptic connections. This proposal fits in with my long-term research objective which is to understand the basic mechanisms of mutual nerve-muscle trophic interactions and the establishment of neuromuscular synapses during the course of embryological development. The results of this study should indicate whether competition among neurons is one of the principles involved in innervation of muscles during embryogenesis. It should also increase our basic understanding of neuromuscular disorders and motor neuron abiotrophies which are clinically very common.
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