This study continues to test the hypothesis that neuromuscular compartments of a single muscle are selectively reestablished following injury. The mouse lateral gastrocnemius muscle is the study model. Two major experiments are proposed. 1. We will transect the parent lateral gastrocnemius-soleus nerve to produce transient injury, then surgically repair 50% of the injured cases by reapposing the proximal and distal stumps in a collagen film wrap. Will the re-innervating axons re-enter their original primary nerve branches? Will they reinnervate the same subvolume of muscle at the same end-plates? Will there be a difference in the surgically repaired cases? 2. We will selectively kill motoneurons which innervate a specific neuromuscular compartment by back-filling these neurons with ricin (a cytotoxic glycoprotein which inhibits protein synthesis). How will other compartment neurons and muscle fibers of the muscle respond to a neighboring compartment whose source of innervation is permanently removed? Tests will be performed on neonatal, juvenile, adult and senescent mice to address questions of age dependency. Subsequently, neurotracer, electrophysiological and fluoro-immunohistochemical methods will be used to compare centrally and peripherally, the control and post-injury organization of neuromuscular compartments. Also, comparisons will be made with data obtained from previous studies in which injury was induced by nerve crush. Under the light microscope, neuromuscular compartment boundaries, fiber type, motoneuron and endplate distributions will be analyzed. Under the electron microscope (scanning and transmission), peripheral nerve axonal profiles, pre- and postsynaptic feature of motor endings and myofibrillary M-band structure of muscle fibers will be analyzed. Results should continue to provide information on (i) morphological changes due to partial, permanent and transient injuries, (ii) patterns of neural outgrowth, including sprouting, (iii) specificity of re- innervation and (iv) possibly the plastic potential of a compartmentalized muscle. Such should be significant in contributing to our knowledge of central and peripheral responses to neuromuscular injuries, including the repair process, and in possibly establishing additional guideline for reparative procedures.
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