TY - JOUR T1 - Motor Learning Promotes Remyelination via New and Surviving Oligodendrocytes JF - bioRxiv DO - 10.1101/2020.01.28.923656 SP - 2020.01.28.923656 AU - Clara M. Bacmeister AU - Helena J. Barr AU - Crystal R. McClain AU - Michael A. Thornton AU - Dailey Nettles AU - Cristin G. Welle AU - Ethan G. Hughes Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/01/29/2020.01.28.923656.abstract N2 - Oligodendrocyte loss in neurological disease leaves axons vulnerable to damage and degeneration, and activity-dependent myelination may represent an endogenous mechanism to improve remyelination following injury. Here, we report that while learning a forelimb reach task transiently suppresses oligodendrogenesis, it subsequently increases OPC differentiation, oligodendrocyte generation, and retraction of pre-existing myelin sheaths in the forelimb region of motor cortex. Immediately following demyelination, motor cortex neurons exhibit hyperexcitability, motor learning is impaired, and behavioral intervention provides no long-term benefit to remyelination. However, partial remyelination restores neuronal and behavioral function. Motor learning following partial remyelination increases oligodendrogenesis and enhances the ability of mature oligodendrocytes to generate new myelin sheaths, resulting in almost double the remyelination of denuded axons relative to untrained controls. Together, our findings demonstrate that the correct timing of behaviorally-induced neuronal circuit activation improves recovery from demyelinating injury via enhanced remyelination from new and surviving oligodendrocytes. ER -