Vesicular glutamate release from axons in white matter.
Vesicular release of neurotransmitter is the universal output signal of neurons in the brain. It is generally believed that fast transmitter release is restricted to nerve terminals that contact postsynaptic cells in the gray matter. Here we show in the rat brain that the neurotransmitter glutamate is also released at discrete sites along axons in white matter in the absence of neurons and nerve terminals. The propagation of single action potentials along axons leads to rapid vesicular release of glutamate, which is detected by ionotropic glutamate receptors on local oligodendrocyte precursor cells. Axonal release of glutamate is reliable, involves highly localized calcium microdomain signaling and is strongly calcium cooperative, similar to vesicle fusion at synapses. This axonal transmitter release represents a widespread mechanism for high-fidelity, activity-dependent signaling at the axon-glia interface in white matter.
Kukley
Maria
M
Experimental Neurophysiology, Department of Neurosurgery, University Clinic Bonn, Germany. maria.kukley@gmx.de
Capetillo-Zarate
Estibaliz
E
Dietrich
Dirk
D
D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D003337:Corpus Callosum / Q000166:cytology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D016253:Microscopy, Immunoelectron / Q000379:methods; D009457:Neuroglia / Q000166:cytology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D019081:O Antigens / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D011073:Polyamines / Q000494:pharmacology; D011509:Proteoglycans / Q000378:metabolism; D011726:Pyridinium Compounds / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D051381:Rats; D013779:Tetrodotoxin / Q000494:pharmacology; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D002118:Calcium; D002614:Chelating Agents; D004533:Egtazic Acid; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D018733:Nicotinic Antagonists; D019081:O Antigens; D011073:Polyamines; D011509:Proteoglycans; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D013779:Tetrodotoxin; D000099216:Chondroitin Sulfate Proteoglycan 4; C073804:FM1 43; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; C034092:delta-philanthotoxin