Myelination induces axonal hotspots of synaptic vesicle fusion that promote sheath growth.

Autor:	Almeida RG; Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK. Electronic address: rafael.g.almeida@ed.ac.uk., Williamson JM; Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK., Madden ME; Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK., Early JJ; Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK., Voas MG; Department of Developmental Biology, Stanford University, Stanford, CA, USA; National Cancer Institute, Frederick, MD, USA., Talbot WS; Department of Developmental Biology, Stanford University, Stanford, CA, USA., Bianco IH; Department of Neuroscience, Physiology and Pharmacology, UCL, London, UK., Lyons DA; Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK. Electronic address: david.lyons@ed.ac.uk.
Jazyk:	angličtina
Zdroj:	Current biology : CB [Curr Biol] 2021 Sep 13; Vol. 31 (17), pp. 3743-3754.e5. Date of Electronic Publication: 2021 Jul 15.
DOI:	10.1016/j.cub.2021.06.036
Abstrakt:	Myelination of axons by oligodendrocytes enables fast saltatory conduction. Oligodendrocytes are responsive to neuronal activity, which has been shown to induce changes to myelin sheaths, potentially to optimize conduction and neural circuit function. However, the cellular bases of activity-regulated myelination in vivo are unclear, partly due to the difficulty of analyzing individual myelinated axons over time. Activity-regulated myelination occurs in specific neuronal subtypes and can be mediated by synaptic vesicle fusion, but several questions remain: it is unclear whether vesicular fusion occurs stochastically along axons or in discrete hotspots during myelination and whether vesicular fusion regulates myelin targeting, formation, and/or growth. It is also unclear why some neurons, but not others, exhibit activity-regulated myelination. Here, we imaged synaptic vesicle fusion in individual neurons in living zebrafish and documented robust vesicular fusion along axons during myelination. Surprisingly, we found that axonal vesicular fusion increased upon and required myelination. We found that axonal vesicular fusion was enriched in hotspots, namely the heminodal non-myelinated domains into which sheaths grew. Blocking vesicular fusion reduced the stable formation and growth of myelin sheaths, and chemogenetically stimulating neuronal activity promoted sheath growth. Finally, we observed high levels of axonal vesicular fusion only in neuronal subtypes that exhibit activity-regulated myelination. Our results identify a novel "feedforward" mechanism whereby the process of myelination promotes the neuronal activity-regulated signal, vesicular fusion that, in turn, consolidates sheath growth along specific axons selected for myelination. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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