Department of Physics, University of California, San Diego, La Jolla, United States.
Elife. 2021 Dec 31;10:e73585. doi: 10.7554/eLife.73585.
Rapid and precise neuronal communication is enabled through a highly synchronous release of signaling molecules neurotransmitters within just milliseconds of the action potential. Yet neurotransmitter release lacks a theoretical framework that is both phenomenologically accurate and mechanistically realistic. Here, we present an analytic theory of the action-potential-triggered neurotransmitter release at the chemical synapse. The theory is demonstrated to be in detailed quantitative agreement with existing data on a wide variety of synapses from electrophysiological recordings and fluorescence experiments . Despite up to ten orders of magnitude of variation in the release rates among the synapses, the theory reveals that synaptic transmission obeys a simple, universal scaling law, which we confirm through a collapse of the data from strikingly diverse synapses onto a single master curve. This universality is complemented by the capacity of the theory to readily extract, through a fit to the data, the kinetic and energetic parameters that uniquely identify each synapse. The theory provides a means to detect cooperativity among the SNARE complexes that mediate vesicle fusion and reveals such cooperativity in several existing data sets. The theory is further applied to establish connections between molecular constituents of synapses and synaptic function. The theory allows competing hypotheses of short-term plasticity to be tested and identifies the regimes where particular mechanisms of synaptic facilitation dominate or, conversely, fail to account for the existing data for the paired-pulse ratio. The derived trade-off relation between the transmission rate and fidelity shows how transmission failure can be controlled by changing the microscopic properties of the vesicle pool and SNARE complexes. The established condition for the maximal synaptic efficacy reveals that no fine tuning is needed for certain synapses to maintain near-optimal transmission. We discuss the limitations of the theory and propose possible routes to extend it. These results provide a quantitative basis for the notion that the molecular-level properties of synapses are crucial determinants of the computational and information-processing functions in synaptic transmission.
快速而精确的神经元通讯是通过在动作电位产生后的短短几毫秒内，高度同步地释放信号分子神经递质来实现的。然而，神经递质释放缺乏一个既具有现象准确性又具有机械现实性的理论框架。在这里，我们提出了一个化学突触上动作电位触发神经递质释放的分析理论。该理论被证明与来自电生理学记录和荧光实验的各种突触的现有数据在细节上定量一致。尽管在释放率方面存在多达十个数量级的差异，但该理论揭示了突触传递遵循一个简单的、普遍的缩放规律，我们通过将来自截然不同的突触的数据从惊人的多样性压缩到一个单一的主曲线上，证实了这一普遍性。这种普遍性与理论能够通过拟合数据，轻松提取唯一识别每个突触的动力学和能量参数的能力相得益彰。该理论提供了一种检测介导囊泡融合的 SNARE 复合物之间协同作用的方法，并在几个现有数据集揭示了这种协同作用。该理论进一步应用于建立突触的分子成分与突触功能之间的联系。该理论允许对短期可塑性的竞争假设进行测试，并确定特定的突触易化机制占主导地位或相反地无法解释现有数据的脉冲比的区域。传输率和保真度之间的权衡关系表明，通过改变囊泡库和 SNARE 复合物的微观性质，可以控制传输失败。最大突触效能的建立条件揭示了某些突触无需精细调整即可保持近乎最佳的传输。我们讨论了该理论的局限性，并提出了可能的扩展途径。这些结果为以下观点提供了定量依据，即突触的分子水平特性是突触传递的计算和信息处理功能的关键决定因素。
