Journal
EXPERIMENTAL NEUROLOGY
Volume 276, Issue -, Pages 41-50Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2015.10.006
Keywords
Myelin; Vesicular release; Action potential; Axons; NMDA; AMPA; Ca2+ imaging; Ryanodine receptor
Categories
Funding
- Canadian Institutes for Health Research (CIHR), Canada Research Chairs, MS Society of Canada, Alberta Heritage Foundation for Medical Research
- CIHR
- T. Chen Fong
- Alberta Innovates Health Solutions
- MS Society of Canada, Canadian Stroke Network Research Summer Studentship
- Alberta Innovates [201400502] Funding Source: researchfish
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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 Ca2+ 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 Ca2+ levels mediated by GluN2D and GIuN3A-containing NMDA receptors. Glutamate is released from axons in a vesicular manner that is tetanus toxin-sensitive. The Ca2+ source for vesicular fusion is provided by ryanodine receptors on axonal Ca2+ stores, controlled by L-type Ca2+ channels that sense depolarization of the internodal axolemma. Genetic ablation of GluN2D and GIuN3A 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. (C) 2015 Elsevier Inc. All rights reserved.
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