Grant: Operating Grant

One of the success stories in treatment of spinal cord injury has been the adoption of active locomotor-based rehabilitation. While the underlying mechanisms may never be fully known, a consensus has emerged that part of the recovery is due to activity-driven reorganization of spinal circuits. These spinal circuits are essential for producing many motor behaviors including walking. Despite the success of these programs, patients do plateau in their recovery over time, and indeed activity-dependent rehabilitation does not work for some patients. It would be beneficial to have drug-based therapies promoting activation of spinal circuits that would accelerate activity-dependent recovery of function. Our work and that of others has established that spinal circuits can be awakened by application of exogenous drugs or by electrical stimulation of nerves. Promising candidates are chemical transmitters (monoamines) that are released by the brain within the spinal cord and normally activate and modulate spinal circuits. Perhaps the biggest impediment to future success is our lack of basic knowledge about the spinal circuits that generate walking and consequently where and how these drugs may be acting. Our work explores this issue using an innovative mouse model. We use mice that 'light up' cells involved in walking. We can then target these cells and circuits to test drug combinations that turn on the dormant walking engine downstream of the injury. Our expectation is that these approaches will lead to new drug-based therapies that will dramatically increase the effectiveness of current rehabilitation strategies.