Several lines of evidence suggest that the number and distribution of axonal contacts on postsynaptic cells are regulated by competitive interactions between axons during development.
The aim of this work is to better understand the developmental strategies that regulate this competition. The studies will utilize new techniques that allow for visualization of individual terminals in living preparations under the light microscope. The normally occurring competitive reduction in the number of terminals that innervate a muscle fiber (synapse elimination) will be followed by viewing terminals of one axon that have been made visible by activity dependent tracer uptake. Preliminary experiments indicate that it is possible (a) to activate an individual identified motor axon and its motor unit in the transversus abdominis muscle of the garter snake by extracellular stimulation, (b) To identify neurally activated nerve terminals in the light microscope using uptake of fluorescein-dextran or a peroxidase enzyme, and (c) to see peroxidase filled processes in vivo by the enzyme mediated conversion of L-DOPA into melanin. Our objective is to use these techniques in order to observe the competitive process which results in the 'capture' of an endplate by one axon. Among the questions this project aims to answer are: (1) Does axonal competition proceed by means of physical contact among terminals or does competition occur at a distance? (2) What is the relationship between the elimination and proliferation of synapses which occur concurrently during development? (3) Does synapse elimination play a role in creating qualitative specificity (e.g., matching of types of motor axon and fiber). Answers to these questions are fundamental to understanding the basis of appropriate connectivity between nerve cells and their targets. The transversus abdominis muscle of the garter snake is an advantageous preparation since it is only one fiber in thickness, enabling excellent visability of all the neuromuscular contacts. Moreover, it contains several types of innervating axons and muscle fibers which are arranged in a stereotyped repeating pattern.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Neurology B Subcommittee 1 (NEUB)
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Washington University
Schools of Medicine
Saint Louis
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