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Motor Learning Promotes Remyelination via New and Surviving Oligodendrocytes

View ORCID ProfileClara M. Bacmeister, View ORCID ProfileHelena J. Barr, Crystal R. McClain, View ORCID ProfileMichael A. Thornton, View ORCID ProfileDailey Nettles, View ORCID ProfileCristin G. Welle, View ORCID ProfileEthan G. Hughes
doi: https://doi.org/10.1101/2020.01.28.923656
Clara M. Bacmeister
1Department of Cell and Developmental Biology, University of Colorado School of Medicine
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Helena J. Barr
1Department of Cell and Developmental Biology, University of Colorado School of Medicine
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Crystal R. McClain
1Department of Cell and Developmental Biology, University of Colorado School of Medicine
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Michael A. Thornton
1Department of Cell and Developmental Biology, University of Colorado School of Medicine
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Dailey Nettles
1Department of Cell and Developmental Biology, University of Colorado School of Medicine
2Department of Neurosurgery, University of Colorado School of Medicine
3Department of Physiology and Biophysics, University of Colorado School of Medicine
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Cristin G. Welle
2Department of Neurosurgery, University of Colorado School of Medicine
3Department of Physiology and Biophysics, University of Colorado School of Medicine
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Ethan G. Hughes
1Department of Cell and Developmental Biology, University of Colorado School of Medicine
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  • For correspondence: ethan.hughes@ucdenver.edu
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Abstract

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.

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Posted January 29, 2020.
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Motor Learning Promotes Remyelination via New and Surviving Oligodendrocytes
Clara M. Bacmeister, Helena J. Barr, Crystal R. McClain, Michael A. Thornton, Dailey Nettles, Cristin G. Welle, Ethan G. Hughes
bioRxiv 2020.01.28.923656; doi: https://doi.org/10.1101/2020.01.28.923656
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Motor Learning Promotes Remyelination via New and Surviving Oligodendrocytes
Clara M. Bacmeister, Helena J. Barr, Crystal R. McClain, Michael A. Thornton, Dailey Nettles, Cristin G. Welle, Ethan G. Hughes
bioRxiv 2020.01.28.923656; doi: https://doi.org/10.1101/2020.01.28.923656

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