Defining and exploiting the plasticity transcriptome to repair the damaged spinal cord

SUMMARY A century of research has shown that the adult central nervous system is incapable of self-repair after injury or disease. Indeed, adults with traumatic spinal cord injuries maintain chronic functional deficits that impact all aspects of their lives. However, increasing evidence suggests that the adult CNS retains some ability to initiate a growth program and functionally re-organize in response to activity, experience and mild trauma and particularly after intensive rehabilitative therapy. In this proposal we have used in vivo viral tracing in combination with FACS and single cell RNA sequencing to develop a comprehensive anatomical and molecular atlas of the adult corticospinal tract (CST). We plan to leverage this atlas to define the molecular mechanisms that drive axon growth in specific subsets of corticospinal tract neurons during rehab in the presence and absence of the axon growth inhibitors nogo receptor-1. We believe that a comprehensive understanding of the intrinsic molecular mechanism that initiates and sustains rehab-mediated axon growth within defined subsets of CST neurons can then be exploited to design novel therapies to repair the acutely and chronically damaged spinal cord.