The goal of this mentored career development award is to enable the candidate?s transition to independence as a physician-scientist studying the connection between plasticity, sleep and stroke. The candidate is an MD, PhD sleep neurologist with a background in engineering, human sleep electrophysiology and how it relates to brain plasticity. The award will help the candidate gain experience in basic genetic, molecular and in-vivo imaging techniques as well as an in-depth knowledge of the cellular and molecular mechanisms involved in plasticity mediated neuronal repair. This award will help the candidate to become an independent physician scientist using sleep as way to accelerate the pace of scientific discovery and its application to the care of individuals with neurological disease. This career development award brings together three experts covering the diverse fields of sleep (Landsness ? PI), plasticity of brain recovery (Lee ? Mentor) and optical neuroimaging (Culver ? Mentor) to tackle this innovative concept and potentially open-up a new field of research. The research environment in which this career development award is proposed is outstanding. Dr. Jin Moo Lee, a translational neuroscientist and vascular neurologist with an interest in the plasticity of stroke recovery, has a long track record of both scientific and mentorship success. Dr. Joe Culver, is a long-time collaborator of the Lee lab and highly experienced in the imaging techniques the candidate will use. Finally, the Washington University neuroscience community emphasizes high quality research, career development of young faculty and collaboration, all keys to his success. An objective of this proposal is to understand the role of slow wave sleep (SWS) in repair and recovery after focal ischemic brain injury. Local SWS is critical for learning-related brain plasticity. Mechanisms involved in brain plasticity have been postulated to be necessary for successful neural repair and recovery after brain injury. Neuronal activity in somatostatinergic interneurons (SOMi) has recently been shown to critically mediate SWS. We propose to 1) determine the role of global SWS in a mouse model of brain repair following focal ischemia (photothrombosis) in somatosensory cortex and 2) locally manipulate SWS (via SOMi using chemogenetics) to determine if modulating local SWS affects cortical remapping, synaptogenesis, and sensorimotor recovery. If the hypothesis is correct, it will show that locally manipulating SWS can selectivity drive plasticity and ultimately recovery from stroke. It will also determine if SOMi might be amenable to targeting and may help shape a novel therapeutic approach to enhancing plasticity and recovery following stroke. This career development award is the ideal platform for the candidate to acquire important training in basic research techniques, deepen his understanding of the role SWS in repair and recovery of stroke, and will launch him towards an independent research career focused on using sleep to aid in care of individuals suffering from stroke.
The research aims proposed in this application focus on a better understanding of the role of slow wave sleep in post-stroke recovery, the leading cause of adult disability in the US with annual incidence of 800,000 and with over 7 million stroke survivors. This research has the potential to clarify the basic mechanisms of how slow wave sleep regulates neuronal repair and recovery after stroke. Ultimately, this knowledge may identify novel therapies that could enhance recovery after stroke, which would greatly improve health for patients, reduce disability, and enrich quality of life.
