A Monte Carlo simulation dissecting quantal release at the calyx of Held
A Monte Carlo simulation dissecting quantal release at the calyx of Held
复制标题
蒙特卡罗模拟剖析了 Held 花萼处的量子释放。
DOI：
10.2741/4360
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发表时间：
2015-06-01
影响因子：
3.1
通讯作者：
Xue, Lei
中科院分区：
文献类型：
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作者：
Guo, Jun;Sun, Zhi-cheng;Xue, Lei
虽然量子释放提供了突触强度的基本控制，但其潜在机制尚不清楚。在这里，我们报告了一个精细的真实的三维囊泡融合模型在花萼型突触。通过细化微观超微结构并结合更新的参数，我们的模型适合于模拟量子释放。首先，我们证实了亲跑融合的存在，并对其在自发和受刺激释放中的百分比给出了合理的估计。其次，我们发现AMPA受体的位置导致mEPSC上升时间的巨大变化。谷氨酸外溢对小囊泡mEPSC衰变时间的影响较小，但对大囊泡mEPSC衰变时间有双峰效应。四是mEPSC上升时间随幅度增大而增加，提示是囊泡大小的作用，而不是谷氨酸浓度的作用。我们还应用我们的模型分析了KCl、CaCl2和synaptotagmin-2触发的胞吐。KCl整体上加速了mEPSCs的释放，而在高钙处理和synaptotagmin-2敲除小鼠中，mEPSCs的释放速度减慢，表明更多的亲跑释放。总之，我们的模型为探索囊泡融合的详细机制提供了一种方便的方法。
Although quantal release provides a basic control of synaptic strength, its underlying mechanisms remain unclear. Here, we report a refined realistic 3D vesicle fusion model at calyx-type synapses. By refining the micro ultrastructure and combining updated parameters, our model is appropriate for simulating quantal release. First, we confirmed the existence of kiss-and-run fusion and gave a justified estimation of its percentage in spontaneous and stimulated release. Second, we found the location of AMPA receptors caused the huge variation in the mEPSC rise time. Third, glutamate spillover only slightly contributed to the mEPSC decay time in small vesicles but caused a dual-peak event in large vesicles. Fourth, mEPSC rise time increased with amplitude, suggesting the contribution of vesicle size, not glutamate concentration. We also applied our model to the analysis of KCl, CaCl2 and synaptotagmin-2 triggered exocytosis. KCl globally accelerated the mEPSCs, whereas mEPSCs were slowed down in high calcium treatments and synaptotagmin-2 knock-out mice, indicating more kiss-and-run release. In summary, our model provides a convenient method for exploring the detailed mechanism of vesicle fusion.