Rehabilitative training interacts with ischemia-instigated spine dynamics to promote a lasting population of new synapses in peri-infarct motor cortex


After subtotal infarcts of primary motor cortex (M1), motor rehabilitative training (RT) promotes improvements in paretic forelimb function that have been linked with its promotion of structural and functional reorganization of peri-infarct cortex, but how the reorganization unfolds is scantly understood. Cortical infarcts also instigate a prolonged period of dendritic spine turnover in peri-infarct cortex. Here we investigated the possibility that synaptic structural responses to RT in peri-infarct cortex reflect, in part, interactions with ischemia instigated spine turnover. This was tested after artery-targeted photothrombotic M1 infarcts or sham procedures in adult (4-mo) C57/BL6 male and female GFP-M line (n = 25) and male YFP-H line (n = 5) mice undergoing RT in skilled reaching or no-training control procedures. Regardless of training condition, spine turnover was increased out to 5 weeks post-infarct relative to sham, as was the persistence of new spines formed within a week post-infarct. However, compared with no-training controls, new spines formed during post-infarct weeks 2-4 in mice undergoing RT persisted in much greater proportions to later time points, by a magnitude that predicted behavioral improvements in the RT group. These results indicate that RT interacts with ischemia-instigated spine turnover to promote preferential stabilization of newly formed spines, which is likely to yield a new population of mature synapses in peri-infarct cortex that could contribute to cortical functional reorganization and behavioral improvement. The findings newly implicate ischemia-instigated spine turnover as a mediator of cortical synaptic structural responses to RT and newly establish the experience-dependency of new spine fates in the post-ischemic turnover context.

Journal article
Journal of Neuroscience