Rapid Ca2+ channel accumulation contributes to cAMP-mediated increase in transmission at hippocampal mossy fiber synapses
Rapid Ca2+ channel accumulation contributes to cAMP-mediated increase in transmission at hippocampal mossy fiber synapses
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DOI：
10.1073/pnas.2016754118
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发表时间：
2021-03-02
影响因子：
11.1
通讯作者：
Sakaba, Takeshi
中科院分区：
文献类型：
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作者：
Fukaya, Ryota;Maglione, Marta;Sakaba, Takeshi
环磷酸腺苷（cAMP）依赖性增强神经递质的释放是重要的更高的大脑功能，如学习和记忆。为了揭示潜在的机制，我们应用成对的前和突触后记录海马苔藓纤维CA 3突触。Ca 2+释放实验并未显示细胞内Ca 2+对cAMP释放递质的敏感性发生变化，但表明释放部位局部Ca 2+浓度增加，但远低于增强前其他突触的Ca 2+浓度。全内反射荧光（TIRF）显微镜显示，在5至10分钟内的释放位点的局部Ca 2+浓度的明显增加，这表明在局部Ca 2+的增加是由快速Ca 2+通道积累的简单机制解释。一致的是，二维时间门控受激发射耗尽显微镜（gSTED）显微镜显示的P/Q-型钙离子通道簇的大小增加附近的释放网站。两者合计，这项研究表明，在海马苔藓纤维-CA 3突触，即积累的活性区Ca 2+通道的cAMP依赖性增加的传输的潜在机制。
The cyclic adenosine monophosphate (cAMP)-dependent potentiation of neurotransmitter release is important for higher brain functions such as learning and memory. To reveal the underlying mechanisms, we applied paired pre- and postsynaptic recordings from hippocampal mossy fiber-CA3 synapses. Ca2+ uncaging experiments did not reveal changes in the intracellular Ca2+ sensitivity for transmitter release by cAMP, but suggested an increase in the local Ca2+ concentration at the release site, which was much lower than that of other synapses before potentiation. Total internal reflection fluorescence (TIRF) microscopy indicated a clear increase in the local Ca2+ concentration at the release site within 5 to 10 min, suggesting that the increase in local Ca2+ is explained by the simple mechanism of rapid Ca2+ channel accumulation. Consistently, two-dimensional time-gated stimulated emission depletion microscopy (gSTED) microscopy showed an increase in the P/Q-type Ca2+ channel cluster size near the release sites. Taken together, this study suggests a potential mechanism for the cAMP-dependent increase in transmission at hippocampal mossy fiber-CA3 synapses, namely an accumulation of active zone Ca2+ channels.