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

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

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71 Scopus citations

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.

Original languageEnglish (US)
Article number306
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Mitew, S., Gobius, I., Fenlon, L. R., McDougall, S. J., Hawkes, D., Xing, Y. L., Bujalka, H., Gundlach, A. L., Richards, L. J., Kilpatrick, T. J., Merson, T. D., & Emery, B. (2018). Pharmacogenetic stimulation of neuronal activity increases myelination in an axon-specific manner. Nature communications, 9(1), [306]. https://doi.org/10.1038/s41467-017-02719-2