Rehabilitation-triggered cortical plasticity after stroke: in vivo imaging at multiple scales
Authors: Allegra Mascaro A.L., Conti E., Lai S., Spalletti C., Di Giovanna AP., Alia C., Panarese A., Sacconi L., Micera S., Caleo M., Pavone FS.
Autors Affiliation: Univ Firenze, Lab Europeo Spettroscopie Nonlineari, Florence, Italy; Scuola Super Sant Anna, Pisa, Italy; CNR, Ist Nanosci, Rome, Italy; Scuola Super Sant Anna, BioRobot Inst, Pisa, Italy; CNR, Ist Nazl Ott, Rome, Italy
Abstract: Neurorehabilitation protocols based on the use of robotic devices provide a highly repeatable therapy and have recently shown promising clinical results. Little is known about how rehabilitation molds the brain to promote motor recovery of the affected limb. We used a custom-made robotic platform that provides quantitative assessment of forelimb function in a retraction test. Complementary imaging techniques allowed us to access to the multiple facets of robotic rehabilitation-induced cortical plasticity after unilateral photothrombotic stroke in mice Primary Motor Cortex (Caudal Forelimb Area – CFA). First, we analyzed structural features of vasculature and dendritic reshaping in the peri-infarct area with two-photon fluorescence microscopy. Longitudinal analysis of dendritic branches and spines of pyramidal neurons suggests that robotic rehabilitation promotes the stabilization of peri-infarct cortical excitatory circuits, which is not accompanied by consistent vascular reorganization towards pre-stroke conditions. To investigate if this structural stabilization was linked to functional remapping, we performed mesoscale wide-field imaging on GCaMP6 mice while performing the motor task on the robotic platform. We revealed temporal and spatial features of the motor-triggered cortical activation, shining new light on rehabilitation-induced functional remapping of the ipsilesional cortex. Finally, by using an all-optical approach that combines optogenetic activation of the contralesional hemisphere and wide-field functional imaging of peri-infarct area, we dissected the effect of robotic rehabilitation on inter-hemispheric cortico-cortical connectivity.
KeyWords: Neural Imaging; Sensor