Quantal analysis estimates docking site occupancy determining short‐term depression at hippocampal glutamatergic synapses
Quantal analysis estimates docking site occupancy determining short‐term depression at hippocampal glutamatergic synapses
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定量分析估计对接位点占用率决定海马谷氨酸突触的短期抑制
DOI：
10.1113/jp282235
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Takafumi Miki
中科院分区：
文献类型：
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作者：
Mamoru Tanaka;Takeshi Sakaba;Takafumi Miki
在融合之前，突触囊泡（SVs）暂停在离散的释放/对接位点。在重复刺激过程中，随着SV的融合和补充，位置占用的可能性发生了变化。占据概率被认为是突触强度的重要决定因素之一，但由于它通常与其他突触参数混合，难以单独估计。因此，位点占用对突触功能的贡献，特别是对突触抑制的贡献，仍然难以捉摸。在这里，我们直接估计了海马苔藓纤维- CA3神经元间突触的占据概率，显示突触抑制，使用反褶积检测到的水泡事件计数统计。我们发现，在3毫米外部钙条件下，该突触具有特别高的占用率（~ 0.85）和高的对接SV释放概率（~ 0.8）。对量子振幅和SV计数的分析表明，量子大小的减少在一定程度上降低了训练中所有反应的振幅，而释放/对接位点数量在训练期间保持不变，表明量子大小和释放/对接位点数量对突触抑制的程度影响不大。模型模拟表明，高释放概率的初始占用和缓慢的补充决定了突触抑制的时间过程。与此一致的是，外部钙浓度的降低降低了占用和释放概率，而降低反过来又减少了凹陷。基于这些结果，我们认为占用概率是海马谷氨酸突触短期突触抑制的关键决定因素。突触囊泡在突触前末端占据释放/对接位点的概率被认为是突触强度的关键决定因素之一，但很难与其他突触参数分开估计。在这里，我们利用反褶积检测到的水泡事件统计数据，直接估计了海马苔藓纤维-神经元间突触的占据概率。我们发现，在高外部钙浓度（[Ca2+]o）条件下，突触具有特别高的占用率（0.85）和高释放概率（0.8），并且这两个参数值都随着[Ca2+]o的变化而变化，形成突触抑制。量子振幅和突触囊泡计数的分析表明，量子大小和释放/对接位点数量对突触抑制的程度影响不大。结果表明，占据概率是海马谷氨酸突触短期突触抑制的关键决定因素。
AbstractBefore fusion, synaptic vesicles (SVs) pause at discrete release/docking sites. During repetitive stimulation, the probability of site occupancy changes following SV fusion and replenishment. The occupancy probability is considered to be one of the crucial determinants of synaptic strength, but it is difficult to estimate separately because it usually blends with other synaptic parameters. Thus, the contribution of site occupancy to synaptic function, particularly to synaptic depression, remains elusive. Here, we directly estimated the occupancy probability at the hippocampal mossy fibre‐CA3 interneuron synapse showing synaptic depression, using statistics of counts of vesicular events detected by deconvolution. We found that this synapse had a particularly high occupancy (∼0.85) with a high release probability of a docked SV (∼0.8) under 3 mmexternal calcium conditions. Analyses of quantal amplitudes and SV counts indicated that quantal size reduction decreased the amplitudes of all responses in a train to a similar degree, whereas release/docking site number was unchanged during trains, suggesting that quantal size and release/docking site number had little influence on the extent of synaptic depression. Model simulations revealed that the initial occupancy with high release probability and slow replenishment determined the time course of synaptic depression. Consistently, decreasing external calcium concentration reduced both the occupancy and release probability, and the reductions in turn produced less depression. Based on these results, we suggest that the occupancy probability is a crucial determinant of short‐term synaptic depression at glutamatergic synapses in the hippocampus.Key pointsThe occupancy probability of a release/docking site by a synaptic vesicle at presynaptic terminals is considered to be one of the crucial determinants of synaptic strength, but it is difficult to estimate separately from other synaptic parameters.Here, we directly estimate the occupancy probability at the hippocampal mossy fibre‐interneuron synapse using statistics of vesicular events detected by deconvolution.We show that the synapses have particularly high occupancy (0.85) with high release probability (0.8) under high external calcium concentration ([Ca2+]o) conditions, and that both parameter values change with [Ca2+]o, shaping synaptic depression.Analyses of the quantal amplitudes and synaptic vesicle counts suggest that quantal sizes and release/docking site number have little influence on the extent of synaptic depression.The results suggest that the occupancy probability is a crucial determinant of short‐term synaptic depression at glutamatergic synapses in the hippocampus.