STROKE-INDUCED FUNCTIONAL REORGANIZATION OF INDIVIDUAL NEURONS AND NEURAL ENSEMBLES IN THE MOUSE PERI-INFARCT MOTOR CORTEX

Once a stroke occurs, victims suffer from lifelong disabilities including the impairment of speech, vision and motor control. No pharmacological therapy is currently available to stimulate the restoration of function after a large stroke. However, in cases of smaller strokes, spontaneous recovery could occur even without therapeutical interventions, while the mechanisms underlying such recovery remain unknown. One critical region for stroke recovery is the peri-infarct area, making it a pivotal candidate to understand fundamental mechanisms of intrinsic rewiring and recoding. Here we trained mice to perform skilled grasping on a ladder wheel during chronic 2photon calcium imaging in the distal primary motor cortex (M1) in the healthy condition and several weeks after a stroke targeting rostral M1. We chronically tracked the functional fate of individual neurons and neuronal populations across stroke recovery, enabling longitudinal assessment of cortical dynamics after stroke. Kinematic analysis of the behavioral performance of gross forelimb movements, revealed an initial loss of motor function followed by spontaneous improvement over time. Longitudinal imaging combined with chemo- and optogenetics manipulations was associated with changes in neuronal population activity during the recovery phase, suggesting adaptive reorganization within peri-infarct motor networks. Together, these findings are consistent with intrinsic plasticity in the motor cortex contributing to spontaneous functional recovery after stroke. Such adaptations on network-level may improve our understandings of recovery mechanisms and help to develop strategies to enhance functional outcome in chronic motor impairments following stroke.