Graduate School of Brain Science, Doshisha University, Kyoto, Japan.
Organization for Research Initiatives and Development, Doshisha University, Kyoto, Japan.
J Physiol. 2021 Dec;599(23):5301-5327. doi: 10.1113/JP282235. Epub 2021 Nov 13.
Before 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 mm external 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 POINTS: The 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 ([Ca ] ) conditions, and that both parameter values change with [Ca ] , 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.
在融合之前，突触小泡 (SV) 在离散的释放/停靠位点处暂停。在重复刺激期间，在 SV 融合和补充后，站点占有率的概率会发生变化。站点占有率被认为是突触强度的关键决定因素之一，但由于它通常与其他突触参数混合在一起，因此很难单独估计。因此，站点占有率对突触功能的贡献，特别是对突触抑制的贡献，仍然难以捉摸。在这里，我们使用通过反卷积检测到的囊泡事件计数的统计信息，直接估计了在显示突触抑制的海马苔藓纤维-CA3 中间神经元突触处的占有率概率。我们发现，在外钙条件下，这种突触的占有率特别高（约 0.85），停靠的 SV 的释放概率也很高（约 0.8）。对量子幅度和 SV 计数的分析表明，量子大小减小会使火车中所有反应的幅度相似地减小，而在火车期间释放/停靠站点数量保持不变，这表明量子大小和释放/停靠站点数量对突触抑制的程度几乎没有影响。模型模拟表明，具有高释放概率和缓慢补充的初始占有率决定了突触抑制的时间过程。一致地，降低外钙浓度会降低占有率和释放概率，进而产生更少的抑制。基于这些结果，我们认为占有率概率是海马体中谷氨酸能突触短期突触抑制的关键决定因素。关键点：突触前末端释放/停靠位点处的突触小泡的占有率被认为是突触强度的关键决定因素之一，但它很难与其他突触参数分开估计。在这里，我们使用通过反卷积检测到的囊泡事件的统计信息直接估计海马苔藓纤维-神经元突触处的占有率概率。我们表明，在高外钙浓度 ([Ca]) 条件下，突触具有特别高的占有率（0.85）和高释放概率（0.8），并且这两个参数值都随 [Ca] 变化，形成突触抑制。对量子幅度和突触囊泡计数的分析表明，量子大小和释放/停靠位点数量对突触抑制的程度影响很小。结果表明，占有率概率是海马体中谷氨酸能突触短期突触抑制的关键决定因素。
