The specific hypothesis that neuromuscular compartments of an individual muscle are selectively reestablished following injury will be tested. The mouse lateral gastrocnemius (LG) muscle is the model for study. Testing will be accomplished by first identifying and characterizing the normal features of compartments of this muscle. Retrograde tracing (horseradish peroxidase, Fluoro-Gold) techniques, electrophysiological (e.g. glycogen depletion) and muscle histochemical methods will be used to this end. Secondly, mechanical and chemical manipulations will be imposed on the parent nerve and its branches to induce damage. Then, the repaired neuromuscular compartments will be identified and characterized. Mechanical manipulations will involve localized extreme compression (crush) of the proximal end of the LG nerve to induce injured axons or, application of a cryoprobe (-70 C). Chemical manipulations will include backfilling with ricin (a cytotoxin) to selectively kill spinal motoneurons. Thirdly, the normal and repaired organization of these compartments will be compared. Results from this study will provide information on (i) degenerative changes due to injury (ii) patterns of neural outgrowth (iii) specificity of reinnervation and (iv) may identify the plastic potential of a compartmentalized muscle. This information should be significant in contributing to our knowledge of neuromuscular disorders due to injury and in possibly establishing guidelines for accelerating the repair process. It should therefore serve as a source for clinicians in rehabilitative medicine and neurology for evaluating and treating patients with neurological injuries.
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