UC San Diego

The reestablishment of functional neural networks is vital to stroke recovery and readily occurs during the post-stroke critical period: a window of heightened neuroplasticity and training sensitivity. Although evidence suggests that neural repair processes are engaged as a part of the obligate response to stroke, the mechanisms of these processes remain unknown. Here, using widefield and 2-photon calcium imaging of awake, behaving mice, we determined that surviving neurons in the perilesional tissue are inactive after stroke. These neurons adapt to this prolonged inactivity after stroke by modifying excitatory synapses to include more NR2B-containing NMDA receptors. The inactivity-mediated increase in NR2B expression is critical for recovery since NR2B antagonism or chemogenetic activation prevents recovery. We extend this logic byalso demonstrating demonstrate that experimental neuronal inactivation can restore the post-stroke critical period in a NR2B-dependent manner. Together, our results identify a novel potential stroke therapy and provide a conceptual framework for post-stroke plasticity and functional recovery.