The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
The molecular physiology of the axo-myelinic synapse
Abstract
Myelinated axons efficiently transmit information over long distances. The apposed myelin sheath confers favorable electrical properties, but restricts access of the axon to its extracellular milieu. Therefore, axonal metabolic support may require specific axo-myelinic communication. Here we explored activity-dependent glutamate-mediated signaling from axon to myelin. 2-Photon microscopy was used to image Ca(2+) changes in myelin in response to electrical stimulation of optic nerve axons ex vivo. We show that optic nerve myelin responds to axonal action potentials by a rise in Ca(2+) levels mediated by GluN2D and GluN3A-containing NMDA receptors. Glutamate is released from axons in a vesicular manner that is tetanus toxin-sensitive. The Ca(2+) source for vesicular fusion is provided by ryanodine receptors on axonal Ca(2+) stores, controlled by L-type Ca(2+) channels that sense depolarization of the internodal axolemma. Genetic ablation of GluN2D and GluN3A subunits results in greater lability of the compact myelin. Our results support the existence of a novel synapse between the axon and its myelin, suggesting a means by which traversing action potentials can signal the overlying myelin sheath. This may be an important physiological mechanism by which an axon can signal companion glia for metabolic support or adjust properties of its myelin in a dynamic manner. The axo-myelinic synapse may contribute to learning, while its disturbances may play a role in the pathophysiology of central nervous system disorders such as schizophrenia, where subtle abnormalities of myelinated white matter tracts have been shown in the human, or to frank demyelinating disorders such as multiple sclerosis.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Optic nerve oligodendrocytes can form axon-myelinic synapses, responding to axonal action potentials via glutamate ionotropic NMDA receptors (24).”
From Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system (2016) · cites this paper as [24]
Citations
Cites
THE USE OF LEAD CITRATE AT HIGH pH AS AN ELECTRON-OPAQUE STAIN IN ELECTRON MICROSCOPY
Reynolds, E. S. (1963) · The Journal of Cell Biology · doi:10.1083/jcb.17.1.208 · Cited by 24,938
Glutamate Receptor Ion Channels: Structure, Regulation, and Function
Traynelis, S. F., Wollmuth, L. P., McBain, C. J., Menniti, F. S., Vance, K. M., Ogden, K. K., Hansen, K. B., Yuan, H., Myers, S. J., & Dingledine, R. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002451 · Cited by 3,568
Biology of Oligodendrocyte and Myelin in the Mammalian Central Nervous System
Baumann, N., & Pham-Dinh, D. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.871 · Cited by 1,828
Plasticity in gray and white: neuroimaging changes in brain structure during learning
Zatorre, R. J., Fields, R. D., & Johansen-Berg, H. (2012) · Nature Neuroscience · doi:10.1038/nn.3045 · Cited by 1,685
Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity
Fünfschilling, U., Supplie, L. M., Mahad, D., Boretius, S., Saab, A. S., Edgar, J., Brinkmann, B. G., Kassmann, C. M., Tzvetanova, I. D., Möbius, W., et al. (2012) · Nature · doi:10.1038/nature11007 · Cited by 1,523
Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain
Gibson, E. M., Purger, D., Mount, C. W., Goldstein, A. K., Lin, G. L., Wood, L. S., Inema, I., Miller, S. E., Bieri, G., Zuchero, J. B., et al. (2014) · Science · doi:10.1126/science.1252304 · Cited by 1,472
White matter in learning, cognition, and psychiatric disorders
Fields, R. D. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.04.001 · Cited by 1,337
Motor skill learning requires active central myelination
McKenzie, I. A., Ohayon, D., Li, H., Paes de Faria, J., Emery, B., Tohyama, K., & Richardson, W. D. (2014) · Science · doi:10.1126/science.1254960 · Cited by 1,177
Axonal Neuregulin-1 Regulates Myelin Sheath Thickness
Michailov, G. V., Sereda, M. W., Brinkmann, B. G., Fischer, T. M., Haug, B., Birchmeier, C., Role, L. W., Lai, C., Schwab, M. H., & Nave, K. (2004) · Science · doi:10.1126/science.1095862 · Cited by 940
Role of Distinct NMDA Receptor Subtypes at Central Synapses
Cull-Candy, S. G., & Leszkiewicz, D. N. (2004) · Science s STKE · doi:10.1126/stke.2552004re16 · Cited by 796
Cited by
Sorted by citations
Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system
Marques, S., Zeisel, A., Codeluppi, S., van Bruggen, D., Mendanha Falcão, A., Xiao, L., Li, H., Häring, M., Hochgerner, H., Romanov, R. A., et al. (2016) · Science · doi:10.1126/science.aaf6463 · Cited by 1,132
“Optic nerve oligodendrocytes can form axon-myelinic synapses, responding to axonal action potentials via glutamate ionotropic NMDA receptors (30).”
Oligodendroglial NMDA receptors regulate glucose import and axonal energy metabolism
Saab, A. S., Tzvetavona, I. D., Trevisiol, A., Baltan, S., Dibaj, P., Kusch, K., Möbius, W., Goetze, B., Jahn, H. M., Huang, W., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.05.016 · Cited by 590
“Recently, axonal activity was shown to induce NMDA receptor-mediated calcium increases in myelin, indicating that adult oligodendrocytes have functional NMDA receptors (Micu et al., 2016).”
InfluentialTranscriptional Convergence of Oligodendrocyte Lineage Progenitors during Development
Marques, S., van Bruggen, D., Vanichkina, D. P., Floriddia, E. M., Munguba, H., Väremo, L., Giacomello, S., Falcão, A. M., Meijer, M., Björklund, Å. K., et al. (2018) · Developmental Cell · doi:10.1016/j.devcel.2018.07.005 · Cited by 290
Remyelination therapies: a new direction and challenge in multiple sclerosis
Plemel, J. R., Liu, W., & Yong, V. W. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.115 · Cited by 293
Self-citationMyelin dynamics: protecting and shaping neuronal functions
Saab, A. S., & Nave, K. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.09.013 · Cited by 270
Metadata
- Authors
- Micu, I., Plemel, J. R., Lachance, C., Proft, J., Jansen, A. J., Cummins, K., van Minnen, J., & Stys, P. K.
- Affiliations
- University of Calgary (CA)
- Corresponding author
- Stys, Peter K.
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 276
- Pages
- 41-50
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W2192308003
- Cited by
- 140
- References
- 58
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 14 · 2023: 7 · 2022: 13 · 2021: 18 · 2020: 11 · 2019: 15 · 2018: 11 · 2017: 21 · 2016: 12
- FWCI
- 6.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alberta Heritage Foundation for Medical Research
- Canadian Institutes of Health Research
- Multiple Sclerosis Society of Canada
- Canada Research Chairs
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Keywords
- myelin sheath, NMDA receptor, GluN2D, GluN3A, glutamate release, action potential, calcium signaling, ryanodine receptor, L-type calcium channels, optic nerve, demyelinating disease, multiple sclerosis, schizophrenia
- MeSH terms
- Animals, Axons, Male, Myelin Sheath, Nerve Fibers, Myelinated, Optic Nerve, Synapses, Receptors, N-Methyl-D-Aspartate, Mice, Knockout, Calcium Signaling, Rats, Long-Evans, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
