Spinal interneuron subpopulations and modular circuits in normal locomotor control and after spinal cord injury

Loss of locomotor activity due to accident or disease is devastating to patients and may lead to early death. Currently, we have limited understanding of the neural circuits that control movement, which hampers efforts to devise better therapeutics to treat loss of motor function. The fundamental goal of my laboratory is to reveal the organization of neural circuits that control normal locomotion in order to identify mechanisms that could be targeted when that behavior is disrupted by injuries and diseases. Currently, we focus on interneuron (IN) populations that form the locomotor circuits in the mouse spinal cord, and aim to reveal the organizational logic and functional roles of these circuits in locomotor control. More importantly, we hope to provide insight into the potential roles of spinal INs in neuroplasticity and recovery after spinal cord injury (SCI). Based on our previous and current studies of one specific IN population, designated V3 INs, as a model system, we predict that spinal IN subpopulations could serve as modular components in locomotor circuits, allowing for task-dependent selection of functionally distinct circuit outputs. These individual modules may function in different aspects of locomotor control and respond differently to SCI and subsequent rehabilitation regimens, knowledge that could be crucial for recovery from SCI. To address these issues, we will employ various genetic and molecular tools in combination with advanced anatomical, electrophysiological, optogenetic, behavioral and computational approaches to define functional V3 IN subpopulations; define task-dependent functional modules of V3 INs in locomotor circuits; and investigate their potential functions in normal locomotion and in SCI.