Functional locomotor recovery in patients with spinal cord injury (SCI) is a realistic possibility given advancements in medical treatment; however, the neural mechanisms that subserve improved motor function are poorly understood. Understanding the interrelationship between lesion severity, sparing of descending systems and locomotor recovery is critical. While greater axonal sparing results in enhanced recovery, the contribution of specific descending systems remains unknown. Furthermore, recent evidence suggests that the relationship between sparing and recovery may not be linear. Should a non-linear relationship exist, only small reparative changes in axon sparing would be needed to produce substantial behavioral improvement. Therefore, we propose to identify specific descending neural substrates associated with locomotor recovery using a clinically relevant animal model of SCI. To conclusively determine the susceptibility of specific descending systems and the existence of a non-linear recovery pattern, we will produce systematic gradations, in contusion severity and examine selected sensory and motor components of locomotor recovery. In addition, we will determine whether axonal sparing distributed throughout multiple nuclei will induce greater locomotor recovery than sparing isolated to one or two specific nuclei. We will compare the motor recovery resulting from distributed sparing following contusion injury to specific sparing from selective funiculotomies. We will also identify the neuroanatomical components needed to produce lasting improvements in over-ground locomotion induced by exercise training after SCI. The critical feature of any rehabilitation is the carry-over of exercise-induced improvements to functionally relevant conditions. We will determine the source and amount of spared descending axons necessary to produce transfer of training from treadmill to over-ground locomotion. It is especially important to understand the transfer of training associated with treadmill locomotion so that new therapeutic interventions target the neural systems most critical for promoting substantial functional recovery.
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