Heckmann Manfred, Pauli Martin
Department of Neurophysiology, Institute for Physiology, Julius-Maximilians-University Würzburg, Würzburg, Germany.
Front Synaptic Neurosci. 2022 May 18;14:901341. doi: 10.3389/fnsyn.2022.901341. eCollection 2022.
The presynaptic active zone (AZ) of chemical synapses is a highly dynamic compartment where synaptic vesicle fusion and neurotransmitter release take place. During evolution the AZ was optimized for speed, accuracy, and reliability of chemical synaptic transmission in combination with miniaturization and plasticity. Single-molecule localization microscopy (SMLM) offers nanometer spatial resolution as well as information about copy number, localization, and orientation of proteins of interest in AZs. This type of imaging allows quantifications of activity dependent AZ reorganizations, e.g., in the context of presynaptic homeostatic potentiation. In combination with high-pressure freezing and optogenetic or electrical stimulation AZs can be imaged with millisecond temporal resolution during synaptic activity. Therefore SMLM allows the determination of key parameters in the complex spatial environment of AZs, necessary for next generation simulations of chemical synapses with realistic protein arrangements.
化学突触的突触前活性区（AZ）是一个高度动态的区室，突触小泡融合和神经递质释放在此发生。在进化过程中，活性区在实现化学突触传递的速度、准确性和可靠性的同时，还兼顾了小型化和可塑性，从而得到了优化。单分子定位显微镜（SMLM）提供纳米级空间分辨率，以及关于活性区中感兴趣蛋白质的拷贝数、定位和方向的信息。这种成像类型能够对活性依赖的活性区重组进行定量分析，例如在突触前稳态增强的情况下。结合高压冷冻以及光遗传学或电刺激，活性区能够在突触活动期间以毫秒级时间分辨率进行成像。因此，单分子定位显微镜能够确定活性区复杂空间环境中的关键参数，这对于下一代具有真实蛋白质排列的化学突触模拟是必不可少的。
