The Role of Intracortical Circuits in Motor Recovery from Spinal Cord Injury

Spinal cord injury interrupts not only the transmission of ascending sensory and descending motor information within the spinal cord, but also disrupts the cortical sensorimotor networks that process this information. Cortical reorganization occurs after SCI and motor maps are shaped through rehabilitation, though the underlying mechanisms remain unknown. Intracortical horizontal connections in primary motor cortex contribute to the plasticity of motor maps. However, the contribution of horizontal connectivity to recovery after SCI is unknown. The overall objective of this proposal is to identify the intracortical circuitry responsible for restoring skilled forelimb function. I will test the central hypothesis that latent horizontal connections from neighboring regions are required for rehabilitation-mediated cortical motor network remodeling after SCI. The rationale for the proposed research is that the knowledge of how the motor cortex incorporates circuit changes after SCI will help us to target new therapies for motor recovery. The following three specific aims are proposed: 1) Determine the changes in endogenous activity of intracortical horizontal connections during rehabilitation-mediated motor recovery from SCI, 2) Determine the structural changes in horizontal connections during recovery from SCI, and 3) Identify the contribution of horizontal connections to motor recovery after SCI. The proposed studies are innovative in that they shift the focus of spinal cord rehabilitation onto the circuit mechanisms of cortical network plasticity and will have far-reaching importance in translating treatments for both acute and chronic injuries to motor networks. The proposed studies are significant because they will elucidate the mechanisms by which circuit remodeling influences recovery and will inform combinatorial strategies that target cortical plasticity in order to fully realize the effects of axonal sprouting and regeneration, cell transplantation, and rehabilitation. At the completion of the proposed studies, my expectation is to have established the role for horizontal connections in rehabilitation-mediated recovery of skilled motor function after SCI. Our expected findings will inform combinatorial strategies that target cortical plasticity in order to fully realize the effects of axonal sprouting and regeneration, cell transplantation, and rehabilitation.