Gibson Erin M, Purger David, Mount Christopher W, Goldstein Andrea K, Lin Grant L, Wood Lauren S, Inema Ingrid, Miller Sarah E, Bieri Gregor, Zuchero J Bradley, Barres Ben A, Woo Pamelyn J, Vogel Hannes, Monje Michelle
Departments of Neurology, Neurosurgery, and Pediatrics, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Science. 2014 May 2;344(6183):1252304. doi: 10.1126/science.1252304. Epub 2014 Apr 10.
Myelination of the central nervous system requires the generation of functionally mature oligodendrocytes from oligodendrocyte precursor cells (OPCs). Electrically active neurons may influence OPC function and selectively instruct myelination of an active neural circuit. In this work, we use optogenetic stimulation of the premotor cortex in awake, behaving mice to demonstrate that neuronal activity elicits a mitogenic response of neural progenitor cells and OPCs, promotes oligodendrogenesis, and increases myelination within the deep layers of the premotor cortex and subcortical white matter. We further show that this neuronal activity-regulated oligodendrogenesis and myelination is associated with improved motor function of the corresponding limb. Oligodendrogenesis and myelination appear necessary for the observed functional improvement, as epigenetic blockade of oligodendrocyte differentiation and myelin changes prevents the activity-regulated behavioral improvement.
中枢神经系统的髓鞘形成需要从少突胶质前体细胞（OPC）产生功能成熟的少突胶质细胞。电活动神经元可能会影响OPC功能，并选择性地指导活跃神经回路的髓鞘形成。在这项研究中，我们对清醒、行为活跃的小鼠运动前皮质进行光遗传学刺激，以证明神经元活动会引发神经祖细胞和OPC的促有丝分裂反应，促进少突胶质细胞生成，并增加运动前皮质深层和皮质下白质内的髓鞘形成。我们进一步表明，这种由神经元活动调节的少突胶质细胞生成和髓鞘形成与相应肢体运动功能的改善有关。少突胶质细胞生成和髓鞘形成似乎是观察到的功能改善所必需的，因为少突胶质细胞分化和髓鞘变化的表观遗传阻断会阻止活动调节的行为改善。
