Adaptation of internal motor copy circuits in recovery after spinal cord injury.

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Abstract: Spinal cord injuries (SCI) affect approximately 100,000 patients each year and causes motor, sensory and autonomic dysfunction. Approximately 55% of all SCIs occur at the cervical level in human patients that effect forelimb. Patients effected by a cervical SCI desire recovery of hand and digit function to improve their current lifestyle. However, the majority of spinal cord injury models study the functional recovery associates with locomotion after thoracic lesions and not skilled forelimb patterning after cervical injuries. In general, skilled forelimb patterning is mediated through the corticospinal tract with support from indirect brainstem regions. Lesions that cut the corticospinal tract show significant loss of forelimb patterning; however, when the indirect pathways are preserved, rehabilitative training supports the recovery of the lost function. We show that this recovery is mediated by C3-C4 propriospinal neurons, a unique propriospinal neuron normally involved in the formation of an internal motor copy to correct movement errors during the movement. In this pathway, error correction is mediated by C3-C4 PN axons terminating onto neurons in the lateral reticular nucleus, a pre-cerebellar nucleus. Information is then routed through the cerebellum where the motor plan is compared to proprioceptive sensory information from the forelimb and back to brainstem motor control regions for execution. We hypothesize that after cervical injury this pathway undergoes rehabilitative adaptation to compensate for loss of the CST. Here we will take a systems approach to interrogate three components required for error correction and adaptation of this pathway. The first aim will examine the integration of information from several forelimb control pathways into the LRN and if modulation of LRN neuronal activity during rehabilitation augments recovery. The second aim will investigate the role of unconscious proprioceptive sensory information in rehabilitative recovery of injury. The third aim, will investigate the cerebellar efferent pathways connecting to know reticular regions involved in forelimb movements to determine their importance in driving recovery and error correction after cervical injury and during rehabilitation. Ultimately, this study will provide essential data to identify the pathways involved in rehabilitative recovery of skilled forelimb patterning after spinal cord injury and if recovery can be enhanced by activity dependent modulation during rehabilitative training.