Farsi Zohreh, Walde Marie, Klementowicz Agnieszka E, Paraskevopoulou Foteini, Woehler Andrew
Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, 10115, Germany.
Institute of Neurophysiology, NeuroCure Cluster of Excellence, Charité-Universitätsmedizin, Berlin, 10115, Germany.
iScience. 2020 Dec 8;24(1):101909. doi: 10.1016/j.isci.2020.101909. eCollection 2021 Jan 22.
Mammalian central synapses exhibit vast heterogeneity in signaling strength. To understand the extent of this diversity, how it is achieved, and its functional implications, characterization of a large number of individual synapses is required. Using glutamate imaging, we characterized the evoked release probability and spontaneous release frequency of over 24,000 individual synapses. We found striking variability and no correlation between action potential-evoked and spontaneous synaptic release strength, suggesting distinct regulatory mechanisms. Subpixel localization of individual evoked and spontaneous release events reveals tight spatial regulation of evoked release and enhanced spontaneous release outside of evoked release region. Using on-stage post hoc immune-labeling of vesicle-associated proteins, Ca-sensing proteins, and soluble presynaptic proteins we were able to show that distinct molecular ensembles are associated with evoked and spontaneous modes of synaptic release.
哺乳动物的中枢突触在信号强度方面表现出巨大的异质性。为了了解这种多样性的程度、其实现方式及其功能意义，需要对大量单个突触进行表征。利用谷氨酸成像技术，我们对超过24000个单个突触的诱发释放概率和自发释放频率进行了表征。我们发现了显著的变异性，且动作电位诱发的突触释放强度与自发突触释放强度之间没有相关性，这表明存在不同的调节机制。对单个诱发和自发释放事件的亚像素定位揭示了诱发释放的紧密空间调节以及在诱发释放区域之外增强的自发释放。通过对囊泡相关蛋白、钙传感蛋白和可溶性突触前蛋白进行台上事后免疫标记，我们能够证明不同的分子组合与突触释放的诱发模式和自发模式相关。
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