Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Antigens / metabolism
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Axons / metabolism*
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Axons / ultrastructure
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Calcium / metabolism
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Chelating Agents / pharmacology
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Corpus Callosum / cytology*
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Egtazic Acid / analogs & derivatives
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Egtazic Acid / pharmacology
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Electric Stimulation / methods
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Excitatory Amino Acid Antagonists / pharmacology
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Glutamic Acid / metabolism*
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In Vitro Techniques
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Membrane Potentials / radiation effects
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Microscopy, Immunoelectron / methods
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Neuroglia / cytology*
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Nicotinic Antagonists / pharmacology
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O Antigens / metabolism
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Patch-Clamp Techniques / methods
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Polyamines / pharmacology
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Proteoglycans / metabolism
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Pyridinium Compounds / metabolism
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Quaternary Ammonium Compounds / metabolism
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Rats
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Tetrodotoxin / pharmacology
Substances
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Antigens
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Chelating Agents
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Excitatory Amino Acid Antagonists
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FM1 43
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Nicotinic Antagonists
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O Antigens
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Polyamines
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Proteoglycans
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Pyridinium Compounds
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Quaternary Ammonium Compounds
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chondroitin sulfate proteoglycan 4
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1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
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Glutamic Acid
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Tetrodotoxin
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Egtazic Acid
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delta-philanthotoxin
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Calcium