Vesicular Glutamate Transporter Expression Ensures High-Fidelity Synaptic Transmission at the Calyx of Held Synapses.

Yutaro Nakakubo, Saeka Abe, Tomofumi Yoshida, Chihiro Takami, Masayuki Isa, Sonja M Wojcik, Nils Brose, Shigeo Takamori, Tetsuya Hori

Cell reports 2020 Aug 18

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Recycling of synaptic vesicles (SVs) at presynaptic terminals is required for sustained neurotransmitter release. Although SV endocytosis is a rate-limiting step for synaptic transmission, it is unclear whether the rate of the subsequent SV refilling with neurotransmitter also influences synaptic transmission. By analyzing vesicular glutamate transporter 1 (VGLUT1)-deficient calyx of Held synapses, in which both VGLUT1 and VGLUT2 are co-expressed in wild-type situation, we found that VGLUT1 loss causes a drastic reduction in SV refilling rate down to ∼25% of wild-type values, with only subtle changes in basic synaptic parameters. Strikingly, VGLUT1-deficient synapses exhibited abnormal synaptic failures within a few seconds during high-frequency repetitive firing, which was recapitulated by manipulating presynaptic Cl- concentrations to retard SV refilling. Our data show that the speed of SV refilling can be rate limiting for synaptic transmission under certain conditions that entail reduced VGLUT levels during development as well as various neuropathological processes. Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Yutaro Nakakubo, Saeka Abe, Tomofumi Yoshida, Chihiro Takami, Masayuki Isa, Sonja M Wojcik, Nils Brose, Shigeo Takamori, Tetsuya Hori. Vesicular Glutamate Transporter Expression Ensures High-Fidelity Synaptic Transmission at the Calyx of Held Synapses. Cell reports. 2020 Aug 18;32(7):108040