Despite the capacity of peripheral nerves to regenerate after injury or disease, functional recovery of the sensory system is only partially realized. The broad objective of this proposal is to determine the cellular mechanisms that constrain recovery of the sensory restoration of normal movement, and its profound ineffectiveness, even long after a cut peripheral nerve has regenerated into its original muscle, results in persistent motor disability. The impotence of sensory feedback from muscle is likely to be explained by limitations in the recovery of sensory transduction in the muscle and possibly by a diminished strength of central synaptic transmission are accounted for, as commonly accepted, by the inability of the sensory nerves to reconnect with their cognate muscle receptors. The absence of direct evidence for and the presence of strong challenges to this premise lead us to hypothesize that simple failure of a muscle afferent to reconnect with the appropriate muscle receptor is neither necessary nor sufficient to explain sensory dysfunction. This central hypothesis will be tested through combined electrophysiological and immunohistological studies of sensory nerves supplying long-term reinnervated muscles in living adult rats and cats.
Three specific aims are proposed to determine whether the reconnection with a muscle receptor fully explains: (1) the normal response properties of some muscle afferents, (2) the abnormal response properties of others, and (3) the central synaptic constraints on recovery of sensory function under conditions in which sensory neuropathies, e.g. Guillain-Baree syndrome, diabetic neuropathy, or chronic inflammatory demyelinating polyneuropathy.
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