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.
In postnatal rodent brain, certain NG2-expressing oligodendroglial precursor cells (OPCs) are contacted by synaptic terminals from local neurons. However, it has remained elusive whether and when NG2(+) cells are integrated into neuronal circuits. Here we use patch-clamp recordings from mitotic cells in murine brain slices to show that, unlike any other cell in the central nervous system (CNS), cortical NG2(+) cells divide and relocate while being linked to synaptic junctions. Together with bromodeoxyuridine (BrdU) labeling, our recordings imply that cellular processes that bear synaptic junctions are surprisingly kept during cytokinesis and are inherited by the daughter cells. Cell cycle time (78 h) and relocation speed (5 microm/day) are slowed, and NG2(+) cells largely divide symmetrically. Inheritance of synapses enables newborn glial cells to establish synaptic connections much faster than newborn neurons and ensures that the entire population of NG2(+) cells is exposed to synaptic signals from local axons. The results suggest that synapses do not only transmit neuronal activity but also act as environmental cues for the development of glial cells. Inheritance of synapses allows for the direct transfer of environmental interactions to clonal descendants of OPCs, which might be important for effective colonization and myelination of the developing brain.
Ca2+ influx into presynaptic terminals via voltage-dependent Ca2+ channels triggers fast neurotransmitter release as well as different forms of synaptic plasticity. Using electrophysiological and genetic techniques we demonstrate that presynaptic Ca2+ entry through Cav2.3 subunits contributes to the induction of mossy fiber LTP and posttetanic potentiation by brief trains of presynaptic action potentials while they do not play a role in fast synaptic transmission, paired-pulse facilitation, or frequency facilitation. This functional specialization is most likely achieved by a localization remote from the release machinery and by a Cav2.3 channel-dependent facilitation of presynaptic Ca2+ influx. Thus, the presence of Cav2.3 channels boosts the accumulation of presynaptic Ca2+ triggering presynaptic LTP and posttetanic potentiation without affecting the low release probability that is a prerequisite for the enormous plasticity displayed by mossy fiber synapses.
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