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 oligodendrocyte precursor cell differentiation, oligodendrocyte generation and myelin sheath remodeling in the forelimb motor cortex. Immediately following demyelination, neurons exhibit hyperexcitability, learning is impaired and behavioral intervention provides no benefit to remyelination. However, partial remyelination restores neuronal and behavioral function, allowing learning to enhance oligodendrogenesis, remyelination of denuded axons and the ability of surviving oligodendrocytes to generate new myelin sheaths. Previously considered controversial, we show that sheath generation by mature oligodendrocytes is not only possible but also increases myelin pattern preservation following demyelination, thus presenting a new target for therapeutic interventions. Together, our findings demonstrate that precisely timed motor learning improves recovery from demyelinating injury via enhanced remyelination from new and surviving oligodendrocytes.

中文翻译：

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运动学习通过新的和存活的少突胶质细胞促进髓鞘再生。

神经疾病中少突胶质细胞的丧失使轴突容易受到损害和变性，而活动依赖性髓鞘形成可能代表了一种改善损伤后髓鞘形成的内源性机制。在这里，我们报告，虽然学习前肢到达任务会暂时抑制少突胶质生成，但随后会增加少突胶质前体细胞的分化，少突胶质细胞的生成和前肢运动皮层中髓鞘的重构。脱髓鞘后，神经元立即表现出过度兴奋性，学习受到损害，行为干预对髓鞘再生没有益处。但是，部分髓鞘再生可恢复神经元和行为功能，从而可以学习增强少突胶质生成，轴突的髓鞘再生和存活的少突胶质细胞产生新的髓鞘的能力。以前被认为是有争议的，我们表明成熟的少突胶质细胞不仅可以产生鞘，而且可以在脱髓鞘后增加髓鞘模式的保存，从而为治疗干预提供了新的靶点。总之，我们的发现表明，精确定时的运动学习可以通过增强新的和存活的少突胶质细胞的髓鞘再生来改善脱髓鞘损伤的恢复。