The long-term goals of this program project are to investigate and to provide new information on factors determining survival, regeneration and recovery of function of spinal cord and spinal nerve neurons after injury. The central theme of the proposed continuation is the cellular and molecular changes induced by vertebrate spinal cord or spinal nerve injury that are associated with regeneration of neuronal processes an recovery of function. In the work outlined, Bullitt's Project examines the possibility that immediate early genes or specific marker proteins can signal neuronal subpopulations in the spinal cord that represent the basis for recovery of sensory function after partial spinal cord injury. Farel's Project addresses the possibility that the dorsal root ganglia (DRGs) contain undifferentiated neuronal precursor cells that augment the complement of functional sensory neurons during normal development and may be induced to differentiate to compensate for losses due to neural injury. Mendell's project takes the issue of neuronal birth and specificity into a different direction in testing the hypothesis that particular factors such as nerve growth factor (NGF) regulate the differentiation of particular types of sensory units of the DRG. Perl's Project explores the possibility that neuropathies involving visceral structures may result from abnormal responsiveness of sensory axons consequent to partial interruption of efferent innervation. The ensemble of these projects attend to two clinically relevant themes: to determine how neuronal characteristics are affected by injury and to explore how these changes can be enlisted to facilitate recovery from neuronal injury.
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