When a peripheral nerve is injured, the relationship between the musculoskeletal system andthe neural circuits in the spinal cord which regulate movement is lost. Axons in the proximal stump ofthe cut nerve can regenerate and can reinnervate peripheral targets, but muscles are oftenreinnervated by different motoneurons than before the injury. Using different paradigms which willenhance the early regeneration of axons in cut nerves exacerbates this loss of topographic specificity.Over time, there is little evidence for remodeling of this innervation pattern. This new relationshipbetween spinal circuits and the musculoskeletal system is a major contributor to the poor functionaloutcomes observed clinically. One potential strategy for improving functional recovery might be toinduce adaptive changes in the spinal circuits themselves, such that an improved functionalrelationship of their outputs to the pattern of reinnervation of the musculoskeletal system might beachieved. In this project, we will investigate the capacity to induce such adaptive changes.. Usingtransection and surgical repair of the rat sciatic nerve, with and without enhancement of early axonregeneration, as a model system, we will study the capacity of the outputs of spinal circuits to adaptspontaneously over time by analyzing the timing of activity of antagonist muscles and ankle jointkinematics during different forms of treadmill locomotion. In addition, two innovative approaches tomodifying the outputs of spinal circuits will be studied. First, we will examine the effect of treadmillexercise during the reinnervation period on the extent to which different reinnervated muscular targetsare activated at functionally appropriate times. By activating motoneurons through spinal circuitsduring treadmill locomotion at a time that regenerating motor and sensory axons are growing andreforming connections with muscles, one might anticipate either that the original reinnervation ofmuscles might be more precise than found without exercise, that the outputs of the spinal circuits willchange in an adaptive manner during the reinnervation process, or both. Second, we will investigatewhether operant conditioning of spinal reflexes can be used to modify the outputs of spinal circuits.After muscles have been reinnervated, spinal reflexes will be shaped to produce functionallyappropriate responses using such conditioning. The effectiveness of this training on the timing ofantagonist muscles during treadmill locomotion will be evaluated. It is anticipated that the results ofthese studies will provide a science base not only for improved rehabilitation treatment of a largepopulation of patients with peripheral nerve injuries but also the treatment of other disorders in whichthe relationship between spinal circuits and the musculoskeletal system has been disrupted and thenre-established.
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