Grant: Project Grant

Over the last decade impressive advances have been made in our understanding of spinal cord injury (SCI) and identification of possible therapies. One of the success stories in treatment of spinal cord injury has been the adoption of active locomotor-based rehabilitation. 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. Rehabilitation appears to work because it provides an excitatory stimulus to spinal cord circuits, allowing networks to be expressed, and remodeled. 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. Another approach is direct activation of descending pathways projecting to the brain. Our work explores this issue by activating orexinergic pathways to the spinal cord which link spinal recovery with motivation. We show that centres within the brain that contain orexin are particularly effective in activating locomotor activity. This raises the possibility that stimulation of these orexin centres could facilitate locomotion in patients with movement disorders.