Intact nerve supply is known to be important to the development and maintenance of muscle. However, the mechanisms underlying nerve- muscle interactions are poorly understood. To examine this issue, a unique case of muscle atrophy following damage to a remote nerve will be studied in a simple, insect system. In the grasshopper, loss of a hind leg by autotomy results in atrophy of undamaged, fully innervated muscles in the thorax. Experimental cutting of nerves and loading or unloading of these muscles indicates that severing the leg nerve during autotomy trans-synaptically induces atrophy of the undamaged thoracic muscles. Staining with antibodies and intracellular recordings from muscles and identified neurons will elucidate cellular changes that precede and accompany atrophy. Selective ablations of sensory neurons will examine the role of orthograde influences in the induction of atrophy. Selective axotomy of leg muscle motoneurons will examine the role of retrograde influences. Selective nerve blockade with tetrodotoxin will test the role of neural impulse activity. Blockade with colchicine will test the role of molecules transported by fast axonal transport maintaining. These studies will advance our understanding of the regulatory interactions among neurons and muscle cells that are crucial for the development and maintenance of their mature form and function.
