Although it is clear that the functional properties of the sensory-motor pathways in the lumbosacra spinal cord that control posture and locomotion are activity-dependent and can even learn to step and to stand, little is known about what features of the activity are critical in defining the motor potential of a completely spinalized animal. In the present proposal, we will examine the level of specificity of the proprioceptive input to the adult mouse spinal cord in learning to step and to stand using adaptive control strategies of robotic devices. We will also determine the feasibility of using a serotonergic agonist, quipazine, to alter the functional state of the spinal cord to facilitate learning to step and stand in the adult spinal mouse. We will also examine whether the quipazine-induced effects are manifested via direct stimulation of central pattern generation or by facilitation of proprioceptive feedback processing. We will use a new generation of robotic devices to facilitate learning to step and to stand. We hypothesize that the combination of the robotic and pharmacological interventions used concomitantly will enable the spinal animal to regain stepping and standing ability to a higher level, more rapidly than has been previously recognized. The results from these studies are expected to demonstrate a new paradigm for optimizing the recovery of motor function in mice that can be readily translated to humans with neuromotor disorder such as spinal cord injury and stroke.
