Journal article

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

NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2018

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 myelinati..

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Grants

Awarded by Multiple Sclerosis Research Australia Postdoctoral Fellowship


Awarded by Australian Research Council Future Fellowship Metal Manufactures Ltd.


Awarded by Australian National Health and Medical Research Council (NHMRC) Career Development Fellowship


Awarded by NHMRC


Awarded by Australian Research Council


Funding Acknowledgements

This work was supported by grants from the Myelin Repair Foundation (to B.E.) and Stem Cells Australia, an Australian Research Council Special Research Initiative (to T.D.M., S.M., T.J.K.). S.M. received support from a Multiple Sclerosis Research Australia Postdoctoral Fellowship (13-015). T.D.M. received support from an Australian Research Council Future Fellowship (FT150100207) Metal Manufactures Ltd. B.E. received support from an Australian National Health and Medical Research Council (NHMRC) Career Development Fellowship (1032833) and a Warren Endowed professorship in Neuroscience Research. A.L.G. received support from a NHMRC Project Grant (1067522). L.J.R. was supported by a NHMRC Principal Research Fellowship and received research grants from the NHMRC (Project Grants 1064174, 1126153) and Australian Research Council (Discovery Project 160103958). L.R.F. was supported by an Australian Postgraduate Research Award and top-up from the Queensland Brain Institute. We would like to thank Dr Matthias Klugmann (UNSW, Sydney, Australia) for his kind gift of the rabbit ASPA antibody.