Synergic effect of optogenetic stimulation and motor training boosts recovery of motor functionality after stroke supported by segregation of motor representation

An ischemic event is followed by extensive changes in cortical excitability involving both hemispheres. Plasticity in the injured hemisphere plays a crucial role in post-stroke motor recovery and is a primary target for rehabilitation therapy. Though stimulation of the ipsilesional motor cortex, especially when paired with motor training, facilitates plasticity and functional restoration, the mechanisms underneath the reshaping of cortical functionality are widely unknown. Here, we designed a protocol of optogenetic stimulation of the peri-infarct region as a neuro-plasticizing treatment coupled with a repetitive motor training. This treatment promoted a generalized recovery in forelimb dexterity and the rescue of the essential features of cortical activation profiles during the execution of the motor training. The present work, by exploiting different approaches, provides a fundamental means to better understand the mechanisms underlying the recovery of motor functionality.