My proposal describes a mentored research and career development plan designed to facilitate my transition to an independent clinician-researcher. During the proposed 5 year plan, I will 1) characterize and begin to mechanistically define a post-stroke period of time during which motor recovery is decreasingly sensitive to motor training and 2) develop my career, skills, and knowledge base as I address this interesting and clinically relevant problem. Notably in human patients, most recovery from motor impairment after stroke occurs in the first month and is currently not the focus of most rehabilitation that predominantly targets function through compensatory strategies. Animal models, which also show the existence of a period of heightened recovery early after stroke, provide the opportunity to test approaches to augment and prolong this period of heightened recovery. Using a mouse model of post-stroke motor recovery, I propose to further define the post-stroke sensitive period by describing how the timing and dose of motor retraining interact to affect motor recovery, how fluoxetine (a commonly used anti-depressant medicine) can modify the sensitive period, and how specific neuronal activity influences this sensitive period. Specific training goals include 1) further development of mouse models in which to study post-stroke recovery, 2) developing a foundation in behavioral statistics, 3) learning advanced fluorescence microscopy, 4) learning in vivo optogenetics (optically controlling neuronal activity in an awake, behaving mouse), 5) translational research strategies, 6) developing an independent program of post-stroke recovery research, and 7) how to obtain independent funding. There is an urgent need to develop innovative approaches to post-stroke rehabilitation because despite improvements in acute stroke care, up to sixty percent of stroke survivors suffer disability in arm or leg use, and up to one-third need placement in a longer term care facility. The training program and mentoring team that I have assembled will help to elucidate important recovery interventions, position me to exploit genetic models that impact neural plasticity, and use cutting edge technology to advance this work as I transition to my independent laboratory.
Ischemic stroke is the most common cause of adult disability. Using a mouse model of stroke motor recovery, this proposal seeks to characterize a post-stroke time window during which motor training is maximally able to affect recovery and to test approaches that might augment and/or prolong this period of heightened recovery.