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• W3028291946 abstract "Synaptic vesicles need to be recycled and refilled rapidly to maintain high-frequency synaptic transmission. However, little is known about the control of neurotransmitter transport into synaptic vesicles, which determines the contents of synaptic vesicles and the strength of synaptic transmission. Here, we report that Na⁺ substantially accumulated in the calyx of Held terminals of juvenile mice of either sex during high-frequency spiking. The activity-induced elevation of cytosolic Na⁺ activated vesicular Na⁺/H⁺ exchanger, facilitated glutamate loading into synaptic vesicles, and increased quantal size of asynchronous released vesicles but did not affect the vesicle pool size or release probability. Consequently, presynaptic Na⁺ increased the EPSCs and was required to maintain the reliable high-frequency signal transmission from the presynaptic calyces to the postsynaptic medial nucleus of the trapezoid body (MNTB) neurons. Blocking Na⁺/H⁺ exchange activity decreased the postsynaptic current and caused failures in postsynaptic firing. Therefore, during high-frequency synaptic transmission, when large amounts of glutamate are released, Na⁺ accumulated in the terminals, activated vesicular Na⁺/H⁺ exchanger, and regulated glutamate loading as a function of the level of vesicle release. <b>SIGNIFICANCE STATEMENT</b> Auditory information is encoded by action potentials (APs) phase-locked to sound frequency at high rates. A large number of synaptic vesicles are released during high-frequency synaptic transmission; accordingly, synaptic vesicles need to be recycled and refilled rapidly. We have recently found that a Na⁺/H⁺ exchanger expressed on synaptic vesicles promotes vesicle filling with glutamate. Here, we showed that when a large number of synaptic vesicles are released during high-frequency synaptic transmission, Na⁺ accumulates in axon terminals and facilitates glutamate uptake into synaptic vesicles. Na⁺ thus accelerates vesicle replenishment and sustains reliable synaptic transmission." @default.
• W3028291946 created "2020-05-29" @default.
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• W3028291946 date "2020-05-19" @default.
• W3028291946 modified "2023-09-26" @default.
• W3028291946 title "Spike Activity Regulates Vesicle Filling at a Glutamatergic Synapse" @default.
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• W3028291946 doi "https://doi.org/10.1523/jneurosci.2945-19.2020" @default.
• W3028291946 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7314407" @default.
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