A Monte Carlo model reveals independent signaling at central glutamatergic synapses
A Monte Carlo model reveals independent signaling at central glutamatergic synapses
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DOI：
10.1016/s0006-3495(02)75248-x
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发表时间：
2002-11-01
影响因子：
3.4
通讯作者：
Sejnowski, TJ
中科院分区：
文献类型：
--
作者：
Franks, KM;Bartol, TM;Sejnowski, TJ
我们已经开发了一个生物药理学现实的受体激活模型，在一个理想化的中央神经元能突触，使用蒙特卡罗技术来模拟随机性质的传输后，释放一个单一的突触囊泡。对于具有80个AMPA和20个NMDA受体的突触，具有3000个谷氨酸分子的单个量子打开大约3个NMDAR和20个AMPAR。开放受体的数量直接随受体总数而变化，开放受体的分数不依赖于共定位的AMPAR和NMDAR的比例。变异性下降，无论是总受体数量或量子大小的增加，和AMPAR和NMDAR反应的变异性之间的差异是由于在突触的受体数量不等。尽管NMDAR对谷氨酸的亲和力比AMPAR高得多，但量子释放导致两种受体类型的占用水平相似。受体激活增加发射分子释放或总受体数，而占用水平只依赖于量子大小。曲折的扩散空间减少了溢出的程度和突触外受体的激活。这些结果支持的结论是，信号是空间独立的内部和之间的中央突触。
We have developed a biophysically realistic model of receptor activation at an idealized central glutamatergic synapse that uses Monte Carlo techniques to simulate the stochastic nature of transmission following release of a single synaptic vesicle. For the a synapse with 80 AMPA and 20 NMDA receptors, a single quantum, with 3000 glutamate molecules, opened approximately 3 NMDARs and 20 AMPARs. The number of open receptors varied directly with the total number of receptors, and the fraction of open receptors did not depend on the ratio of co-localized AMPARs and NMDARs. Variability decreased with increases in either total receptor number or quantal size, and differences between the variability of AMPAR and NMDAR responses were due solely to unequal numbers of receptors at the synapse. Despite NMDARs having a much higher affinity for glutamate than AMPARs, quantal release resulted in similar occupancy levels in both receptor types. Receptor activation increased with number of transmitter molecules released or total receptor number, whereas occupancy levels were only dependent on quantal size. Tortuous diffusion spaces reduced the extent of spillover and the activation of extrasynaptic receptors. These results support the conclusion that signaling is spatially independent within and between central glutamatergic synapses.