In vivo optical imaging of cortical plasticity induced by rehabilitation after stroke

In my PhD thesis I have studied the changes in functional and structural plasticity induced by a photothrombotic stroke in mouse primary motor cortex. In order to dissect the multiple aspects consequent to the damage we exploit fluorescent imaging techniques that allow to investigate the functional and structural rearrangement of the cortex at different scale, from the entire hemisphere, with wide-field calcium imaging, up to the single synapse with two-photon microscopy. To promote a functional recovery of the mouse forelimb we applied different rehabilitative strategies in order to both foster the stabilization of regions of the cortex linked to the stroke core, and stimulate the remodelling of peri-infarct areas. We took advantage of a robotic platform (M-Platform), developed by our collaborator in Pisa, to perform the rehabilitation of mouse forelimb through a repetitive motor training. Together with this approach we applied different strategies to mould cortical activity. We temporary inhibited the healthy primary motor cortex, with an intracortical injection of Botulin Neuro Toxin E, in order to counterbalance the iper-excitability of the healthy hemisphere and to promote the structural and functional remodelling of the peri-infarct cortex. This combined rehabilitative protocol promotes the recovery of cortical maps of activation during motor training and the rewiring of interhemispheric connectivity, both from functional and structural level. Then we applied an optogenetic approach as a pro-plasticizing treatment by stimulating with light the region of the cortex surrounding the damage. By coupling this treatment with an intense motor training on the M-Platform we observed a generalized recovery of forelimb functionality in terms of manual dexterity and cortical profiles of activation. In this study, we have shown that different rehabilitative protocols that combines repetitive motor training and neuronal modulation of specific cortical regions induce a synergic effect on neuronal plasticity that promotes the recovery of structural features of healthy neuronal networks.