Vesicular release of glutamate from unmyelinated axons in white matter.
Directed fusion of transmitter-laden vesicles enables rapid intercellular signaling in the central nervous system and occurs at synapses within gray matter. Here we show that action potentials also induce the release of glutamate from axons in the corpus callosum, a white matter region responsible for interhemispheric communication. Callosal axons release glutamate by vesicular fusion, which induces quantal AMPA receptor-mediated currents in NG2(+) glial progenitors at anatomically distinct axo-glial synaptic junctions. Glutamate release from axons was facilitated by repetitive stimulation and could be inhibited through activation of metabotropic autoreceptors. Although NG2(+) cells form associations with nodes of Ranvier in white matter, measurements of conduction velocity indicated that unmyelinated fibers are responsible for glutamatergic signaling with NG2(+) glia. This activity-dependent secretion of glutamate was prevalent in the developing and mature mouse corpus callosum, indicating that axons within white matter both conduct action potentials and engage in rapid neuron-glia communication.
Ziskin
Jennifer L
JL
Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe St., WBSB 813, Baltimore, Maryland 21205, USA.
Nishiyama
Akiko
A
Rubio
Maria
M
Fukaya
Masahiro
M
Bergles
Dwight E
DE
D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000235:genetics / Q000378:metabolism; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000166:cytology*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018942:Macrolides / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron / Q000379:methods; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism* / Q000648:ultrastructure; D009457:Neuroglia / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D008164:Luminescent Proteins; D018942:Macrolides; D011509:Proteoglycans; D020796:Receptor, Platelet-Derived Growth Factor alpha; D050598:Vesicular Glutamate Transport Protein 1; D000099216:Chondroitin Sulfate Proteoglycan 4; C493465:Slc17a7 protein, mouse; C413663:fluorescent protein 583; C040929:bafilomycin A1