Pharmacogenetic stimulation of neuronal activity increases myelination in an axon-specific manner

药物遗传学刺激神经元活动以轴突特异性方式增加髓鞘形成

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作者:Stanislaw Mitew, Ilan Gobius, Laura R Fenlon, Stuart J McDougall, David Hawkes, Yao Lulu Xing, Helena Bujalka, Andrew L Gundlach, Linda J Richards, Trevor J Kilpatrick, Tobias D Merson, Ben Emery

Abstract

Mounting evidence suggests that neuronal activity influences myelination, potentially allowing for experience-driven modulation of neural circuitry. The degree to which neuronal activity is capable of regulating myelination at the individual axon level is unclear. Here we demonstrate that stimulation of somatosensory axons in the mouse brain increases proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) within the underlying white matter. Stimulated axons display an increased probability of being myelinated compared to neighboring non-stimulated axons, in addition to being ensheathed with thicker myelin. Conversely, attenuating neuronal firing reduces axonal myelination in a selective activity-dependent manner. Our findings reveal that the process of selecting axons for myelination is strongly influenced by the relative activity of individual axons within a population. These observed cellular changes are consistent with the emerging concept that adaptive myelination is a key mechanism for the fine-tuning of neuronal circuitry in the mammalian CNS.

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