Functional Circuit Remapping After Stroke

Following ischemic stroke, many patients exhibit partial spontaneous recovery, suggesting that the brain has endogenous mechanisms to recover lost functions. There has been considerable interest in harnessing this process of remapping for therapeutic purposes, especially after the failure of neuroprotective strategies in stroke. However, evidence for remapping from neuroimaging and neurophysiologic studies on human stroke patients has been contradictory and difficult to interpret, in part due to the stochastic nature of human stroke. Thus, how specific changes in neuronal circuits mediate improvement in function and recovery after stroke remains a major gap in our understanding of remapping. Traditional approaches to studying remapping in humans (e.g., fMRI, PET) lack the temporal and spatial resolution to precisely address this question.  At the same time, more recent techniques for assessing remapping with single cell resolution have yet to be rigorously applied to experimental mouse models of stroke. We are utilizing a multi-modal imaging approach in mice, including two-photon calcium imaging, genetic labeling of active neurons, and chemogenetics to define both the local and global changes in neural circuits that mediate functional remapping and recovery after stroke. These studies will fill essential gaps in our knowledge and are highly relevant for current and future translational studies targeted to improve recovery after stroke.