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.
Integrity signals
Registry
Cites
Statistics
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?
Optic nerve oligodendrocytes can form axon-myelinic synapses, responding to axonal action potentials via glutamate ionotropic NMDA receptors.
“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]
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 804 · see citing works
Uptake of Glutamate into Synaptic Vesicles by an Inorganic Phosphate Transporter
Bellocchio, E. E., Reimer, R. J., Fremeau, R. T., & Edwards, R. H. (2000) · Science · doi:10.1126/science.289.5481.957 · Cited by 795 · see citing works
Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits
Chatterton, J. E., Awobuluyi, M., Premkumar, L. S., Takahashi, H., Talantova, M. V., Shin, Y., Cui, J., Tu, S., Sevarino, K. A., Nakanishi, N., et al. (2002) · Nature · doi:10.1038/nature715 · Cited by 695 · see citing works
Astrocytes promote myelination in response to electrical impulses
Ishibashi, T., Dakin, K. A., Stevens, B., Lee, P. R., Kozlov, S. V., Stewart, C. L., & Fields, R. D. (2006) · Neuron · doi:10.1016/j.neuron.2006.02.006 · Cited by 689 · see citing works
Control of local protein synthesis and initial events in myelination by action potentials
Wake, H., Lee, P. R., & Fields, R. D. (2011) · Science · doi:10.1126/science.1206998 · Cited by 636 · see citing works
Altered neuregulin 1–erbB4 signaling contributes to NMDA> receptor hypofunction in schizophrenia
Hahn, C.-G., Wang, H.-Y., Cho, D.-S., Talbot, K., Gur, R. E., Berrettini, W. H., Bakshi, K. P., Kamins, J., Borgmann‐Winter, K. E., Siegel, S. J., et al. (2006) · Nature Medicine · doi:10.1038/nm1418 · Cited by 564 · see citing works
NMDA receptors are expressed in developing oligodendrocyte processes and mediate injury
Salter, M. G., & Fern, R. F. (2005) · Nature · doi:10.1038/nature04301 · Cited by 556 · see citing works
NMDA receptors mediate calcium accumulation in myelin during chemical ischaemia
Micu, I., Jiang, Q., Coderre, E., Ridsdale, A., Zhang, L., Woulfe, J., Yin, X., Trapp, B. D., McRory, J. E., Rehak, R., et al. (2005) · Nature · doi:10.1038/nature04474 · Cited by 504 · see citing works
Self-citationVesicular release of glutamate from unmyelinated axons in white matter
Ziskin, J. L., Nishiyama, A., Rubio, M. E., Fukaya, M., & Bergles, D. E. (2007) · Nature Neuroscience · doi:10.1038/nn1854 · Cited by 476 · see citing works
Assembly of CNS Myelin in the Absence of Proteolipid Protein
Klugmann, M., Schwab, M. H., Pühlhofer, A., Schneider, A., Zimmermann, F., Griffiths, I. R., & Nave, K. (1997) · Neuron · doi:10.1016/s0896-6273(01)80046-5 · Cited by 472 · see citing works
Vesicular glutamate release from axons in white matter
Kukley, M., Capetillo‐Zarate, E., & Dietrich, D. (2007) · Nature Neuroscience · doi:10.1038/nn1850 · Cited by 460 · see citing works
Cryosectioning and immunolabeling
Slot, J. W., & Geuze, H. J. (2007) · Nature Protocols · doi:10.1038/nprot.2007.365 · Cited by 444 · see citing works
Jiang, D., Xiao, B., Yang, D., Wang, R., Choi, P. M. C., Zhang, L., Cheng, H., & Chen, S. R. W. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402388101 · Cited by 441 · see citing works
DTI and MTR abnormalities in schizophrenia: Analysis of white matter integrity
Kubicki, M. R., Park, H., Westin, C., Nestor, P. G., Mulkern, R. V., Maier, S. E., Niznikiewicz, M. A., Connor, E. E., Levitt, J. J., Frumin, M., et al. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.03.026 · Cited by 433 · see citing works
Structure and function of neuronal Ca2+ channels and their role in neurotransmitter release.
Catterall, W. (1998) · Cell Calcium · doi:10.1016/s0143-4160(98)90055-0 · Cited by 397 · see citing works
Myelination in the absence of myelin-associated glycoprotein
Li, C. C., Tropak, M. B., Gerlai, R. T., Clapoff, S., Abramow-Newerly, W., Trapp, B. D., Peterson, A. C., & Roder, J. (1994) · Nature · doi:10.1038/369747a0 · Cited by 380 · see citing works
Barrett, E. F., & Barrett, J. N. (1982) · The Journal of Physiology · doi:10.1113/jphysiol.1982.sp014064 · Cited by 375 · see citing works
Tetanus toxin action: Inhibition of neurotransmitter release linked to synaptobrevin proteolysis
Link, E., Edelmann, L., Chou, J. H., Binz, T., Yamasaki, S., Eisel, U., Baumert, M., Südhof, T. C., Niemann, H., & Jahn, R. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)92305-h · Cited by 349 · see citing works
Neuregulin and BDNF Induce a Switch to NMDA Receptor-Dependent Myelination by Oligodendrocytes
Lundgaard, I., Luzhynskaya, A., Stockley, J. H., Wang, Z., Evans, K. A., Swire, M., Volbracht, K., Gautier, H. O. B., Franklin, R. J. M., ffrench‐Constant, C., et al. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001743 · Cited by 340 · see citing works
Patneau, D. K., Wright, P. W., Winters, C. A., Mayer, M. L., & Gallo, V. (1994) · Neuron · doi:10.1016/0896-6273(94)90277-1 · Cited by 314 · see citing works
Synaptic vesicles immunoisolated from rat cerebral cortex contain high levels of glutamate
Burger, P. M., Mehl, E., Cameron, P. L., Maycox, P. R., Baumert, M., Lottspeich, F., Camilli, P. V. D., & Jahn, R. (1989) · Neuron · doi:10.1016/0896-6273(89)90240-7 · Cited by 299 · see citing works
Signals to promote myelin formation and repair
Taveggia, C., Feltri, M. L., & Wrabetz, L. G. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.37 · Cited by 281 · see citing works
Rat optic nerve: electrophysiological, pharmacological and anatomical studies during development
Foster, R. E., Connors, B. W., & Waxman, S. G. (1982) · Developmental Brain Research · doi:10.1016/0165-3806(82)90005-0 · Cited by 278 · see citing works
Imaging synaptic vesicle exocytosis and endocytosis with FM dyes
Gaffield, M. A., & Betz, W. J. (2006) · Nature Protocols · doi:10.1038/nprot.2006.476 · Cited by 268 · see citing works
Carvedilol and its new analogs suppress arrhythmogenic store overload–induced Ca2+ release
Zhou, Q., Xiao, J., Jiang, D., Wang, R., Vembaiyan, K., Wang, A., Smith, C., Xie, C., Chen, W., Zhang, J., et al. (2011) · Nature Medicine · doi:10.1038/nm.2406 · Cited by 256 · see citing works
Neurotransmitter receptors in the life and death of oligodendrocytes
Káradóttir, R. T., & Attwell, D. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.08.070 · Cited by 252 · see citing works
Court, F. A., Hendriks, W. T. J., MacGillavry, H. D., Álvarez, J., & van Minnen, J. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2429-08.2008 · Cited by 239 · see citing works
Stys, P. K., Ransom, B. R., & Waxman, S. G. (1991) · Brain Research · doi:10.1016/0006-8993(91)91154-s · Cited by 195 · see citing works
Self-citationOuardouz, M., Nikolaeva, M. A., Coderre, E., Zamponi, G. W., McRory, J. E., Trapp, B. D., Yin, X., Wang, W., Woulfe, J., & Stys, P. K. (2003) · Neuron · doi:10.1016/j.neuron.2003.08.016 · Cited by 191 · see citing works
Self-citationDe Biase, L. M., Kang, S. H., Baxi, E. G., Fukaya, M., Pucak, M. L., Mishina, M., Calabresi, P. A., & Bergles, D. E. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.2455-11.2011 · Cited by 161 · see citing works
Berger, S., & Bartsch, D. (2014) · Cell and Tissue Research · doi:10.1007/s00441-014-1936-3 · Cited by 143 · see citing works
N-Methyl-D-aspartate Receptors: Subunit Assembly and Trafficking to the Synapse
Prybylowski, K., & Wenthold, R. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.r300029200 · Cited by 137 · see citing works
Presynaptic calcium stores and synaptic transmission
Collin, T., Marty, A., & Llano, I. (2005) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2005.05.003 · Cited by 134 · see citing works
Neurotransmitter signaling in white matter
Butt, A. M., Fern, R. F., & Matute, C. (2014) · Glia · doi:10.1002/glia.22674 · Cited by 133 · see citing works
LOCALIZED INTRACELLULAR CALCIUM SIGNALING IN MUSCLE: Calcium Sparks and Calcium Quarks
Ernst Niggli, A. (1999) · Annual Review of Physiology · doi:10.1146/annurev.physiol.61.1.311 · Cited by 131 · see citing works
Glutamate receptors on myelinated spinal cord axons: I. GluR6 kainate receptors
Ouardouz, M., Coderre, E., Basak, A., Chen, A. A., Zamponi, G. W., Hameed, S., Rehak, R., Yin, X., Trapp, B. D., & Stys, P. K. (2009) · Annals of Neurology · doi:10.1002/ana.21533 · Cited by 107 · see citing works
Self-citationLarocca, J. N., & Norton, W. T. (2006) · Current Protocols in Cell Biology · doi:10.1002/0471143030.cb0325s33 · Cited by 105 · see citing works
Glutamate receptors on myelinated spinal cord axons: II. AMPA and GluR5 receptors
Ouardouz, M., Coderre, E., Zamponi, G. W., Hameed, S., Yin, X., Trapp, B. D., & Stys, P. K. (2009) · Annals of Neurology · doi:10.1002/ana.21539 · Cited by 104 · see citing works
Self-citationExcitatory Glycine Responses of CNS Myelin Mediated by NR1/NR3 “NMDA” Receptor Subunits
Piña-Crespo, J., Talantova, M. V., Micu, I., States, B. A., Chen, H.-S. V., Tu, S., Nakanishi, N., Tong, G., Zhang, D., Heinemann, S. F., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1593-10.2010 · Cited by 102 · see citing works
Self-citationDepolarizing afterpotentials in myelinated axons of mammalian spinal cord
Blight, A. R., & Someya, S. (1985) · Neuroscience · doi:10.1016/0306-4522(85)90118-6 · Cited by 89 · see citing works
Real-time measurement of free Ca2+ changes in CNS myelin by two-photon microscopy
Micu, I., Ridsdale, A., Zhang, L., Woulfe, J., McClintock, J., Brantner, C. A., Andrews, S., & Stys, P. K. (2007) · Nature Medicine · doi:10.1038/nm1568 · Cited by 78 · see citing works
Self-citationGuo, F., Maeda, Y., Ko, E. M., Delgado, M., Horiuchi, M., Soulika, A., Miers, L., Burns, T., Itoh, T., Shen, H., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.4073-11.2012 · Cited by 76 · see citing works
Lagopoulos, J., Hermens, D. F., Hatton, S. N., Tobias‐Webb, J., Griffiths, K. R., Naismith, S. L., Scott, E. M., & Hickie, I. B. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059108 · Cited by 66 · see citing works
Gagliardi, S., Gatti, P. A., Belfiore, P., Zocchetti, A., Clarke, G. D., & Farina, C. (1998) · Journal of Medicinal Chemistry · doi:10.1021/jm9707838 · Cited by 60 · see citing works
Calcium‐permeable presynaptic AMPA receptors in cerebellar molecular layer interneurones
Rossi, B., Maton, G., & Collin, T. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.159921 · Cited by 46 · see citing works
Functional glutamate transport in rodent optic nerve axons and glia
Arranz, A. M., Hussein, A., Alix, J. J. P., Pérez‐Cerdá, F., Allcock, N., Matute, C., & Fern, R. F. (2008) · Glia · doi:10.1002/glia.20703 · Cited by 45 · see citing works
Hirano, A., Becker, N. H., & Zimmerman, H. M. (1969) · Journal of Histochemistry & Cytochemistry · doi:10.1177/17.8.512 · Cited by 44 · see citing works
Why do oligodendrocyte lineage cells express glutamate receptors?
Kołodziejczyk, K., Saab, A. S., Nave, K., & Attwell, D. (2010) · F1000 Biology Reports · doi:10.3410/b2-57 · Cited by 37 · see citing works
Ridsdale, A., Micu, I., & Stys, P. K. (2004) · Applied Optics · doi:10.1364/ao.43.001669 · Cited by 16 · see citing works
Self-citation
Flagged first, then by citations
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 1,246 · see citing works
“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 · see citing works
“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 · see citing works
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 281 · see citing works
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 259 · see citing works
On Myelinated Axon Plasticity and Neuronal Circuit Formation and Function
Almeida, R. G., & Lyons, D. A. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.3185-16.2017 · Cited by 221 · see citing works
Emerging roles of GluN3-containing NMDA receptors in the CNS
Pérez-Otaño, I., Larsen, R. S., & Wesseling, J. F. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.92 · Cited by 214 · see citing works
Periods of synchronized myelin changes shape brain function and plasticity
de Faria, O., Pivoňková, H., Varga, B. V., Timmler, S., Evans, K. A., & Káradóttir, R. T. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00917-2 · Cited by 193 · see citing works
Ca2+ activity signatures of myelin sheath formation and growth in vivo
Baraban, M., Koudelka, S., & Lyons, D. A. (2017) · Nature Neuroscience · doi:10.1038/s41593-017-0040-x · Cited by 193 · see citing works
Axo-myelinic neurotransmission: a novel mode of cell signalling in the central nervous system
Micu, I., Plemel, J. R., Caprariello, A. V., Nave, K., & Stys, P. K. (2017) · Nature reviews. Neuroscience · doi:10.1038/nrn.2017.128 · Cited by 162 · see citing works
Self-citationIntrinsic and adaptive myelination—A sequential mechanism for smart wiring in the brain
Bechler, M. E., Swire, M., & ffrench‐Constant, C. (2017) · Developmental Neurobiology · doi:10.1002/dneu.22518 · Cited by 149 · see citing works
Mechanisms of glutamate toxicity in multiple sclerosis: biomarker and therapeutic opportunities
Macrez, R., Stys, P. K., Vivien, D., Lipton, S. A., & Docagne, F. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)30165-x · Cited by 130 · see citing works
Self-citationOligodendrocytes express synaptic proteins that modulate myelin sheath formation
Hughes, A. N., & Appel, B. (2019) · Nature Communications · doi:10.1038/s41467-019-12059-y · Cited by 128 · see citing works
Neuron-Oligodendrocyte Interactions in the Structure and Integrity of Axons
Duncan, G. J., Simkins, T., & Emery, B. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.653101 · Cited by 121 · see citing works
Heterogeneity of Astrocytes in Grey and White Matter
Köhler, S., Winkler, U., & Hirrlinger, J. (2021) · Neurochemical Research · doi:10.1007/s11064-019-02926-x · Cited by 123 · see citing works
Oligodendrocyte–axon metabolic coupling is mediated by extracellular K+ and maintains axonal health
Looser, Z. J., Faik, Z., Ravotto, L., Zanker, H. S., Jung, R. B., Werner, H. B., Ruhwedel, T., Möbius, W., Bergles, D. E., Barros, L. F., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-023-01558-3 · Cited by 120 · see citing works
Movement and structure of mitochondria in oligodendrocytes and their myelin sheaths
Rinholm, J. E., Vervaeke, K., Tadross, M. R., Tkachuk, A. N., Kopek, B. G., Brown, T. A., Bergersen, L. H., & Clayton, D. A. (2016) · Glia · doi:10.1002/glia.22965 · Cited by 102 · see citing works
Oligodendrocytes: Myelination, Plasticity, and Axonal SupportPreprint
Simons, M., Gibson, E. M., & Nave, K. (2024) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a041359 · Cited by 99 · see citing works
Expanding the function of oligodendrocytes to brain energy metabolism
Nave, K., Asadollahi, E., & Sasmita, A. O. (2023) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2023.102782 · Cited by 89 · see citing works
Functional myelin in cognition and neurodevelopmental disorders
Khelfaoui, H., Ibaceta-González, C., & Angulo, M. C. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05222-2 · Cited by 83 · see citing works
Piezo channels contribute to the regulation of myelination in Schwann cells
Acheta, J., Bhatia, U., Jeanette, H., Hong, J., Rich, K., Close, R., Bechler, M. E., Belin, S., & Poitelon, Y. (2022) · Glia · doi:10.1002/glia.24251 · Cited by 84 · see citing works
Pease-Raissi, S. E., & Chan, J. R. (2021) · Neuron · doi:10.1016/j.neuron.2021.02.003 · Cited by 85 · see citing works
Calcium Signaling in the Oligodendrocyte Lineage: Regulators and Consequences
Paez, P. M., & Lyons, D. A. (2020) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-100719-093305 · Cited by 82 · see citing works
Axonal Regulation of Central Nervous System Myelination: Structure and Function
Klingseisen, A., & Lyons, D. A. (2017) · The Neuroscientist · doi:10.1177/1073858417703030 · Cited by 77 · see citing works
Mechanisms of axonal support by oligodendrocyte-derived extracellular vesicles
Krämer‐Albers, E., & Werner, H. B. (2023) · Nature reviews. Neuroscience · doi:10.1038/s41583-023-00711-y · Cited by 78 · see citing works
Simkins, T., Duncan, G. J., & BOURDETTE, D. N. (2021) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-021-01110-5 · Cited by 74 · see citing works
Vesicular glutamate release from central axons contributes to myelin damage
Doyle, S., Hansen, D. B., Vella, J., Bond, P., Harper, G. M., Zammit, C., Valentino, M., & Fern, R. F. (2018) · Nature Communications · doi:10.1038/s41467-018-03427-1 · Cited by 73 · see citing works
Roles of glial ion transporters in brain diseases
Song, S., Luo, L., Sun, B., & Sun, D. (2019) · Glia · doi:10.1002/glia.23699 · Cited by 72 · see citing works
Glial Cell AMPA Receptors in Nervous System Health, Injury and Disease
Ceprián, M., & Fulton, D. J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20102450 · Cited by 70 · see citing works
Foster, A. Y., Bujalka, H., & Emery, B. (2019) · Glia · doi:10.1002/glia.23629 · Cited by 65 · see citing works
Store-operated calcium entry is essential for glial calcium signalling in CNS white matter
Papanikolaou, M., Lewis, A., & Butt, A. M. (2017) · Brain Structure and Function · doi:10.1007/s00429-017-1380-8 · Cited by 68 · see citing works
Sapkota, K., Mao, Z., Synowicki, P., Lieber, D., Liu, M., Ikezu, T., Gautam, V., & Monaghan, D. T. (2015) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.115.230391 · Cited by 64 · see citing works
Fernández-Montoya, J., Avendaño, C., & Negredo, P. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms19010069 · Cited by 63 · see citing works
High-Frequency Microdomain Ca2+ Transients and Waves during Early Myelin Internode Remodeling
Battefeld, A., Popovic, M. A., de Vries, S. I., & Kole, M. H. P. (2019) · Cell Reports · doi:10.1016/j.celrep.2018.12.039 · Cited by 63 · see citing works
Spitzer, S. O., Volbracht, K., Lundgaard, I., & Káradóttir, R. T. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.06.014 · Cited by 62 · see citing works
White Matter Plasticity Keeps the Brain in Tune: Axons Conduct While Glia Wrap
Chorghay, Z., Káradóttir, R. T., & Ruthazer, E. S. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00428 · Cited by 62 · see citing works
Myelination induces axonal hotspots of synaptic vesicle fusion that promote sheath growth
Almeida, R., Williamson, J., Madden, M., Early, J. J., Voas, M. G., Talbot, W. S., Bianco, I. H., & Lyons, D. A. (2021) · Current Biology · doi:10.1016/j.cub.2021.06.036 · Cited by 57 · see citing works
Gallego-Delgado, P., James, R., Browne, E., Meng, J., Umashankar, S., Tan, L., Picón, C., Mazarakis, N., Faisal, A., Howell, O., et al. (2020) · PLoS Biology · doi:10.1371/journal.pbio.3001008 · Cited by 45 · see citing works
CNS myelination requires VAMP2/3-mediated membrane expansion in oligodendrocytes
Lam, M., Takeo, K., Almeida, R., Cooper, M. H., Wu, K., Iyer, M., Kantarci, H., & Zuchero, J. B. (2022) · Nature Communications · doi:10.1038/s41467-022-33200-4 · Cited by 55 · see citing works
Neuron-oligodendroglia interactions: Activity-dependent regulation of cellular signaling
Thornton, M. A., & Hughes, E. G. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.134916 · Cited by 54 · see citing works
Advances in myelinating glial cell development
Herbert, A. L., & Monk, K. R. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2016.11.003 · Cited by 47 · see citing works
Bordeleau, M., de Cossío, L. F., Lacabanne, C., Savage, J. C., Vernoux, N., Chakravarty, M. M., & Tremblay, M. (2021) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2021.100281 · Cited by 46 · see citing works
NMDA Receptors: Power Switches for Oligodendrocytes
Krasnow, A. M., & Attwell, D. (2016) · Neuron · doi:10.1016/j.neuron.2016.06.023 · Cited by 43 · see citing works
Fairless, R., Bading, H., & Diem, R. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.741280 · Cited by 41 · see citing works
Brain incoming call from glia during neuroinflammation: Roles of extracellular vesicles
D’Egidio, F., Castelli, V., d’Angelo, M., Ammannito, F., Quintiliani, M., & Cimini, A. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106663 · Cited by 39 · see citing works
Glutamate transporters: Expression and Function in Oligodendrocytes
Suárez-Pozos, E., Thomason, E. J., & Fuss, B. (2019) · Neurochemical Research · doi:10.1007/s11064-018-02708-x · Cited by 34 · see citing works
Neuroglial interactions underpinning myelin plasticity
de Faria, O., Pama, E., Evans, K. A., Luzhynskaya, A., & Káradóttir, R. T. (2017) · Developmental Neurobiology · doi:10.1002/dneu.22539 · Cited by 38 · see citing works
Kula, B., Chen, T., & Kukley, M. (2019) · Glia · doi:10.1002/glia.23617 · Cited by 35 · see citing works
Barron, T., & Kim, J. H. (2019) · Glia · doi:10.1002/glia.23670 · Cited by 35 · see citing works
Paes-Colli, Y., Aguiar, A. F. L., Isaac, A. R., Ferreira, B. K., Campos, R. M. P., Trindade, P. M. P., Reis, R. A. D. M., & Sampaio, L. D. S. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.917164 · Cited by 38 · see citing works
Toward identifying key mechanisms of progression in multiple sclerosis
Husseini, L., Geladaris, A., & Weber, M. S. (2023) · Trends in Neurosciences · doi:10.1016/j.tins.2023.11.005 · Cited by 35 · see citing works
Calcium Signaling in Neurons and Glial Cells: Role of Cav1 channels
Alves, V. S., Alves-Silva, H. S., Orts, D. J. B., Ribeiro-Silva, L., Arcisio-Miranda, M., & Oliveira, F. A. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.09.041 · Cited by 34 · see citing works
Boscia, F., Elkjaer, M. L., Illés, Z., & Kukley, M. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.685703 · Cited by 33 · see citing works
The Role of Glial Cells in the Pathophysiology of Epilepsy
Onat, F., Andersson, M., & Çarçak, N. (2025) · Cells · doi:10.3390/cells14020094 · Cited by 34 · see citing works
Neuronal activity disrupts myelinated axon integrity in the absence of NKCC1b
Marshall-Phelps, K. L., Kegel, L., Baraban, M., Ruhwedel, T., Almeida, R., Rubio-Brotons, M., Klingseisen, A., Benito-Kwiecinski, S. K., Early, J. J., Bin, J. M., et al. (2020) · The Journal of Cell Biology · doi:10.1083/jcb.201909022 · Cited by 33 · see citing works
Hyperperfusion of Frontal White and Subcortical Gray Matter in Autism Spectrum Disorder
Peterson, B. S., Zargarian, A., Peterson, J. B., Goh, S., Sawardekar, S., Williams, S., Lythgoe, D. J., Zelaya, F. O., & Bansal, R. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.11.026 · Cited by 33 · see citing works
Ionotropic glutamate receptors activate cell signaling in response to glutamate in Schwann cells
Campana, W. M., Mantuano, E., Azmoon, P., Henry, K. W., Banki, M. A., Kim, J. H., Pizzo, D. P., & Gonias, S. L. (2017) · The FASEB Journal · doi:10.1096/fj.201601121r · Cited by 31 · see citing works
Late functional improvement after lacunar stroke: a population-based study
Ganesh, A., Gutnikov, S. A., Rothwell, P. M., & Study, F. T. O. V. (2018) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2018-318434 · Cited by 31 · see citing works
Cuprizone-induced Demyelination in Mouse Brain is not due to Depletion of Copper
Morgan, M. L., Teo, W., Hernandez, Y., Brideau, C., Cummins, K., Kuipers, H. F., & Stys, P. K. (2022) · ASN NEURO · doi:10.1177/17590914221126367 · Cited by 31 · see citing works
Self-citationPathogenicinflammation in the CNS of mice carrying humanPLP1mutations
Groh, J., Friedman, H. C., Orel, N., Ip, C. W., Fischer, S., Spahn, I., Schäffner, E., Hörner, M., Stadler, D., Buttmann, M., et al. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw296 · Cited by 31 · see citing works
Ion Channels as New Attractive Targets to Improve Re-Myelination Processes in the Brain
Cherchi, F., Bulli, I., Venturini, M., Pugliese, A. M., & Coppi, E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147277 · Cited by 26 · see citing works
Tang, X., Li, Z., Zhang, W., & Yao, Z. (2019) · Nitric Oxide · doi:10.1016/j.niox.2019.07.006 · Cited by 27 · see citing works
Saab, A. S., & Nave, K. (2016) · Nature · doi:10.1038/nature16865 · Cited by 26 · see citing works
Valný, M., Honsa, P., Waloschková, E., Matušková, H., Kriška, J., Kirdajová, D., Androvic, P., Valihrach, L., Kubista, M., & Anděrová, M. (2018) · Glia · doi:10.1002/glia.23301 · Cited by 26 · see citing works
Cai, Y., Pinheiro‐de‐Sousa, I., Slobodyanyuk, M., Chen, F., Huynh, T., Kanyo, J. E., Tang, P., Fuentes, L. A., Braker, A., Welch, R., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-01973-8 · Cited by 32 · see citing works
The role of astrocytes from synaptic to non-synaptic plasticity
Sanz-Gálvez, R., Falardeau, D., Kolta, A., & Inglebert, Y. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1477985 · Cited by 25 · see citing works
Tau-Mediated Dysregulation of Neuroplasticity and Glial Plasticity
Koller, E. J., & Chakrabarty, P. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00151 · Cited by 22 · see citing works
Interaction of Myelin Basic Protein with Myelin-like Lipid Monolayers at Air–Water Interface
Widder, K., Träger, J., Kerth, A., Harauz, G., & Hinderberger, D. (2018) · Langmuir · doi:10.1021/acs.langmuir.8b00321 · Cited by 21 · see citing works
Late functional improvement and 5-year poststroke outcomes: a population-based cohort study
Ganesh, A., Luengo-Fernández, R., & Rothwell, P. M. (2020) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2019-322365 · Cited by 22 · see citing works
Tong, J., Zhou, Y., Huang, J., Zhang, P., Fan, F., Chen, S., Tian, B., Cui, Y., Tian, L., Tan, S., et al. (2021) · Schizophrenia Bulletin · doi:10.1093/schbul/sbab003 · Cited by 21 · see citing works
Emerging concepts in oligodendrocyte and myelin formation, inputs from the zebrafish model
Masson, M. L. P., & Nait‐Oumesmar, B. (2023) · Glia · doi:10.1002/glia.24336 · Cited by 22 · see citing works
Functional ionotropic glutamate receptors on peripheral axons and myelin
Christensen, P. C., Welch, N. C., Brideau, C., & Stys, P. K. (2016) · Muscle & Nerve · doi:10.1002/mus.25078 · Cited by 21 · see citing works
Self-citationIonotropic glutamate receptor expression in human white matter
Christensen, P. C., Samadi‐Bahrami, Z., Pavlov, V., Stys, P. K., & Moore, G. R. W. (2016) · Neuroscience Letters · doi:10.1016/j.neulet.2016.07.030 · Cited by 21 · see citing works
Self-citationMyelin plasticity, neural activity, and traumatic neural injury
Kondiles, B. R., & Horner, P. J. (2017) · Developmental Neurobiology · doi:10.1002/dneu.22540 · Cited by 19 · see citing works
Oligodendrocyte Physiology Modulating Axonal Excitability and Nerve Conduction
Yamazaki, Y. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-32-9636-7_9 · Cited by 19 · see citing works
Bamm, V. V., Henein, M., Sproul, S. L. J., Lanthier, D. K., & Harauz, G. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.08.022 · Cited by 20 · see citing works
Serdar, M., Herz, J., Kempe, K., Winterhager, E., Jastrow, H., Heumann, R., Felderhoff‐Müser, U., & Bendix, I. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00175 · Cited by 19 · see citing works
Intrinsic organization of the corpus callosum
Barbaresi, P., Mara Fabri, C., Lorenzi, T., Sagrati, A., & Morroni, M. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2024.1393000 · Cited by 18 · see citing works
Maintenance mechanisms of circuit-integrated axons
Mariano, V., Domıńguez-Iturza, N., Neukomm, L. J., & Bagni, C. (2018) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2018.08.007 · Cited by 17 · see citing works
Tian, N., Hanson, K., Canty, A. J., Vickers, J. C., & King, A. E. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14909 · Cited by 15 · see citing works
Bergaglio, T., Luchicchi, A., & Schenk, G. J. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.610295 · Cited by 15 · see citing works
New views on the complex interplay between degeneration and autoimmunity in multiple sclerosis
Stys, P. K., Tsutsui, S., Gafson, A., Hart, B. A. ‘., Belachew, S. M., & Geurts, J. J. G. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1426231 · Cited by 12 · see citing works
Self-citationCharacterization of cell type-specific S100B expression in the mouse olfactory bulb
Su, X., Vasilkovska, T., Fröhlich, N. T., & Garaschuk, O. (2021) · Cell Calcium · doi:10.1016/j.ceca.2020.102334 · Cited by 10 · see citing works
Turan, F., Yilmaz, Ö., Schünemann, L., Lindenberg, T. T., Kalanithy, J. C., Harder, A., Ahmadi, S., Duman, T., MacDonald, R. B., Winter, D., et al. (2021) · Journal of Neuroscience Research · doi:10.1002/jnr.24940 · Cited by 11 · see citing works
Meijns, N. R. C., Blokker, M., Idema, S., ’t Hart, B. A., Veta, M., Ettema, L., van Iersel, J., Zhang, Z., Schenk, G. J., Groot, M. L., et al. (2025) · PLOS ONE · doi:10.1371/journal.pone.0310663 · Cited by 10 · see citing works
Vervust, W., Safaei, S., Witschas, K., Leybaert, L., & Ghysels, A. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2422437122 · Cited by 9 · see citing works
Kukley, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24044138 · Cited by 10 · see citing works
Micu, I., Brideau, C., Li, L., & Stys, P. K. (2017) · Neurophotonics · doi:10.1117/1.nph.4.2.025002 · Cited by 10 · see citing works
Self-citationOligodendrocytes, BK channels and the preservation of myelin
Rupnik, M., Baker, D., & Selwood, D. L. (2021) · F1000Research · doi:10.12688/f1000research.53422.2 · Cited by 10 · see citing works
All-optical observation on activity-dependent nanoscale dynamics of myelinated axons
Kwon, J., Lee, S., Jo, Y., & Choi, M. (2023) · Neurophotonics · doi:10.1117/1.nph.10.1.015003 · Cited by 9 · see citing works
Wu, X., Wang, Z., Li, H., 谢学顺, Wu, J., Shen, H., Li, X., Wang, Z., & Chen, G. (2021) · Frontiers of Medicine · doi:10.1007/s11684-021-0879-9 · Cited by 8 · see citing works
The Leukocentric Theory of Neurological Disorder: A Manifesto
Fern, R. F. (2017) · Neurochemical Research · doi:10.1007/s11064-017-2279-8 · Cited by 8 · see citing works
Multiple sclerosis: what have we learned and can we still learn from electron microscopy
Oost, W., Meilof, J. F., & Baron, W. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-05690-0 · Cited by 7 · see citing works
Cytoskeletal Regulation of Oligodendrocyte Differentiation and Myelination
Brown, T. L., & Verden, D. R. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.1398-17.2017 · Cited by 7 · see citing works
Axonal neurotransmitter release in the regulation of myelination
Marshall-Phelps, K. L., & Almeida, R. (2024) · Bioscience Reports · doi:10.1042/bsr20231616 · Cited by 6 · see citing works
A myelinic channel system for motor-driven organelle transportPreprint
Chapple, K. J., Green, T. R. F., Wirth, S., Chen, Y.-H., Gerwig, U. C., Aicher, M. L., Kim, Y., Komarek, L., Brown, A. M., Crawford, C. L., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.02.591488 · Cited by 6 · see citing works
Papanikolaou, M., & Butt, A. M. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-805088-0.00003-7 · Cited by 7 · see citing works
Oligodendrocytes, BK channels and remyelination
Rupnik, M., Baker, D., & Selwood, D. L. (2021) · F1000Research · doi:10.12688/f1000research.53422.1 · Cited by 9 · see citing works
Peterson, B. S., Li, J. S., Trujillo, M., Sawardekar, S., Balyozian, D., Bansal, S., Sun, B. F., Marcelino, C., Nanda, A., Xu, T., et al. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02961-5 · Cited by 5 · see citing works
Axo-vascular coupling mediated by oligodendrocytesPreprint
Restrepo, A., Trevisiol, A., Restrepo-Arango, C., Depp, C., Sasmita, A. O., Keller, A., Tzvetanova, I. D., Hirrlinger, J., & Nave, K. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.06.16.495900 · Cited by 5 · see citing works
- 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 · 2015: 1
- 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
