Nonsynaptic junctions on myelinating glia promote preferential myelination of electrically active axons
Open accessAbstract
The myelin sheath on vertebrate axons is critical for neural impulse transmission, but whether electrically active axons are preferentially myelinated by glial cells, and if so, whether axo-glial synapses are involved, are long-standing questions of significance to nervous system development, plasticity and disease. Here we show using an in vitro system that oligodendrocytes preferentially myelinate electrically active axons, but synapses from axons onto myelin-forming oligodendroglial cells are not required. Instead, vesicular release at nonsynaptic axo-glial junctions induces myelination. Axons releasing neurotransmitter from vesicles that accumulate in axon varicosities induces a local rise in cytoplasmic calcium in glial cell processes at these nonsynaptic functional junctions, and this signalling stimulates local translation of myelin basic protein to initiate myelination.
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Inhibition of vesicular release from neurons to mature oligodendrocytes impairs myelination in vitro.
“Inhibition of vesicular release from neurons to mature oligodendrocytes impairs myelination, both in vitro (Wake et al., 2015 ; Wake, Lee, & Fields, 2011 ) and in vivo (Hines, Ravanelli, Schwindt, Scott, & Appel, 2015 ; Mensch et al., 2015 ).”
From Motor learning requires myelination to reduce asynchrony and spontaneity in neural activity (2020) · cites this paper as Wake et al., 2015
In Results, under “Preferential myelination of electrically active axons” (page unavailable), the paper reports substantially fewer and shorter myelin segments on axons whose vesicular release was inhibited in vitro. However, the experiment added oligodendrocyte precursor cells to the neuronal cultures and assessed myelination after they differentiated; it did not specifically inhibit release to oligodendrocytes that were already mature. (LLM, conf=0.83)
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References 26 · Cited by 244
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- Authors
- Wake, H., Ortiz, F. C., Woo, D. H., Lee, P. R., Angulo, M. C., & Fields, R. D.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Fields, R. Douglas
- Venue
- Nature Communications
- Published
- 2015-08-04
- Volume
- 6
- Issue
- 1
- Pages
- 7844-7844
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4532789
- OpenAlex
- W2272917511
- Cited by
- 244
- References
- 26
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 33 · 2023: 13 · 2022: 15 · 2021: 21 · 2020: 23 · 2019: 30 · 2018: 28 · 2017: 26 · 2016: 25 · 2015: 4
- FWCI
- 11.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques
- Agence Nationale de la Recherche (R14193KK)
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- myelination, oligodendrocytes, axonal varicosities, calcium signaling, myelin basic protein, local translation, glial cells
- MeSH terms
- Action Potentials, Animals, Axons, Calcium, Myelin Basic Protein, Exocytosis, Gene Expression Regulation, Intercellular Junctions, Myelin Sheath, Neuroglia, Neurons, Oligodendroglia, Signal Transduction, Neurotransmitter Agents, Calcium Signaling, Mice, In Vitro Techniques
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