Regulation of Quantal Size by Presynaptic Mechanisms

Regulation of Quantal Size by Presynaptic Mechanisms
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突触前机制对量子大小的调节

DOI:
10.1515/revneuro.2000.11.2-3.159
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发表时间:
2000
影响因子:
4.1
通讯作者:
E. Pothos
E. Pothos
中科院分区:
医学3区
文献类型:
--
作者:
D. Sulzer;E. Pothos

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量子大小通常被建模为不变的,尽管现在已经确定在胞吐作用期间每个突触小泡释放的递质分子的数量可以在中枢和外周突触中进行调节。在这篇综述中,我们提出了为什么突触前改变的量子大小对于提供突触外神经递质的社会突触很重要。回顾了当前用于测量量子大小的技术,特别关注电流分析法,这是第一种直接测量分子数量和突触前量子释放动力学的方法,以及中枢神经系统多巴胺神经元末梢。回顾了改变突触前位点量子大小的已知干预措施,并将其分类为(1)跨囊泡自由能梯度的改变,(2)囊泡递质转运蛋白活性的调节,(3)融合孔动力学的调节,(4)改变递质脱颗粒,以及(5)突触囊泡体积的变化。每个量子释放的分子数量的调节是左旋多巴和安非他明药物作用机制的基础,并且似乎可能与正常突触修饰和疾病状态有关。讨论了用于检查量子大小和数据表示的统计分析。我们提供了有关执行非参数重采样统计分析、两个总体的 Kolmogorov-Smirnov 检验以及使用电子表格程序进行随机游走模拟的详细信息。
Quantal size is often modeled as invariant, although it is now well established that the number of transmitter molecules released per synaptic vesicle during exocytosis can be modulated in central and peripheral synapses. In this review, we suggest why presynaptically altered quantal size would be important at social synapses that provide extrasynaptic neurotransmitter. Current techniques used to measure quantal size are reviewed with particular attention to amperometry, the first approach to provide direct measurement of the number of molecules and kinetics of presynaptic quantal release, and to CNS dopamine neuronal terminals. The known interventions that alter quantal size at the presynaptic locus are reviewed and categorized as (1) alteration of transvesicular free energy gradients, (2) modulation of vesicle transmitter transporter activity, (3) modulation of fusion pore kinetics, (4) altered transmitter degranulation, and (5) changes in synaptic vesicle volume. Modulation of the number of molecules released per quantum underlies mechanisms of drug action of L-DOPA and the amphetamines, and seems likely to be involved in both normal synaptic modification and disease states. Statistical analysis for examining quantal size and data presentation is discussed. We include detailed information on performing nonparametric resampling statistical analysis, the Kolmogorov-Smirnov test for two populations, and random walk simulations using spreadsheet programs.
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