All-Optical Rehabilitation Promotes Motor Recovery in a Mouse Model of Stroke

Neuro-rehabilitative research is developing novel strategies to enhance the effectiveness of rehabilitation after stroke by combining physical therapy and plasticizing treatment. Previous studies have shown that the peri-infarct area spontaneously undergoes active remodeling after stroke and this lead to the remapping of cortical areas. It was already reported that repeated neuronal optogenetic stimulation of the peri-lesioned area induces a significant improvement in cerebral blood flow and neurovascular coupling response enhances the recovery of somatosensory cortical circuit function and limb sensorimotor abilities. Here we apply an optogenetic approach, that allows the manipulation of targeted cell populations in the peri-lesioned region, to promote the activation of peri-infarct neurons. We repeatedly stimulated Channelrhodopsin2-transfected neurons with a 473 nm laser five days a week for a month. We further combined optogenetic stimulation and motor training on a robotic platform (M-Platform). The robotic device for rehabilitation of the injured forelimb was integrated within a wide-field microscope, allowing simultaneous mesoscale calcium imaging of cortical activation on Thy1-GCaMP6f mice and recording of forces applied by the injured forelimb during the training sessions. Through behavioral analysis, we show that both strategies trigger a consistent improvement of forelimb functionality. Nevertheless, the combined therapy induces a significant and anticipated recovery of motor function compared to the single treatments.