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.
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We thank S. Schoch for discussions and comments on the manuscript and for sharing reagents; D. Thal and J. Bedorf for help with electron microscopy; R. Buettner and D. Thal for sharing equipment; B. Stallcup and B. Zalc for providing antibodies. This study was supported by Deutsche Forschungsgemeinschaft (SFB TR3, DI 853/2) and University Clinic Bonn grants (BONFOR). We thank P. Stausberg and K. Neitzert for technical assistance.
The authors declare no competing financial interests.
Supplementary Fig. 1
Estimation of the size of the readily releasable pool and of the vesicular release probability. (PDF 145 kb)
Supplementary Fig. 2
A fit of a sum of convolved miniature AGC distributions to the distribution of minimal stimulation amplitudes yields probabilities consistent with a simple binomial process. (PDF 139 kb)
Supplementary Fig. 3
Calcium microdomains trigger axonal transmitter release. Estimation of the distance between calcium channels and synaptic vesicles. (PDF 108 kb)
Supplementary Fig. 4
Typical current patterns of callosal OPCs and pyramidal neurons recorded in whole cell voltage clamp mode. (PDF 100 kb)
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Kukley, M., Capetillo-Zarate, E. & Dietrich, D. Vesicular glutamate release from axons in white matter. Nat Neurosci 10, 311–320 (2007). https://doi.org/10.1038/nn1850
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