Vesicular Glutamate Transporter Expression Ensures High-Fidelity Synaptic Transmission at the Calyx of Held Synapses
Vesicular Glutamate Transporter Expression Ensures High-Fidelity Synaptic Transmission at the Calyx of Held Synapses
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DOI：
10.1016/j.celrep.2020.108040
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发表时间：
2020-08-18
期刊：
影响因子：
8.8
通讯作者：
Hori, Tetsuya
中科院分区：
文献类型：
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作者：
Nakakubo, Yutaro;Abe, Saeka;Hori, Tetsuya
突触前末端突触囊泡（SVs）的循环是神经递质持续释放所必需的。尽管SV内吞作用是突触传递的限速步骤，但尚不清楚随后的SV再填充神经递质的速率是否也会影响突触传递。通过分析野生型情况下VGLUT1和VGLUT2共表达的Held突触花萼中vesicular glutamate transporter 1 （VGLUT1）缺失的情况，我们发现VGLUT1缺失导致SV再填充率急剧下降，降至野生型值的25%左右，突触基本参数仅发生细微变化。引人注目的是，在高频重复放电过程中，vglut1缺陷突触在几秒钟内表现出异常的突触失效，这是通过操纵突触前Cl-浓度来延缓SV再填充来重演的。我们的数据表明，在发育过程中VGLUT水平降低以及各种神经病理过程的某些条件下，SV再填充的速度可能是突触传递的速率限制。
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 similar 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.