Superresolution imaging of chemical synapses in the brain.
Superresolution imaging of chemical synapses in the brain.
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DOI：
10.1016/j.neuron.2010.11.021
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发表时间：
2010-12-09
期刊：
影响因子：
16.2
通讯作者：
Zhuang, Xiaowei
中科院分区：
文献类型：
--
作者：
Dani, Adish;Huang, Bo;Bergan, Joseph;Dulac, Catherine;Zhuang, Xiaowei
确定突触的分子结构需要纳米级的图像分辨率和特定的分子识别，这项任务到目前为止已经挑战了许多传统的成像方法。在这里，我们提出了一种超分辨率荧光成像方法来可视化大脑中突触的分子结构。利用多色三维随机光学重建显微镜，可以纳米级的精度测量突触蛋白的分布。此外，广域、体积成像方法能够高通量地、定量地分析来自不同大脑区域的大量突触。为了证明这种方法的能力，我们已经确定了突触前活动区的十个蛋白质成分的组织和突触后的密度。突触形态、神经递质受体组成和受体分布在突触之间和跨不同脑区都有差异。与光遗传学的结合进一步允许在单一突触水平上解决与突触可塑性相关的分子事件。
Determination of the molecular architecture of synapses requires nanoscopic image resolution and specific molecular recognition, a task that has so far defied many conventional imaging approaches. Here we present a super-resolution fluorescence imaging method to visualize the molecular architecture of synapses in the brain. Using multicolor, three-dimensional stochastic optical reconstruction microscopy, the distributions of synaptic proteins can be measured with nanometer precision. Furthermore, the wide-field, volumetric imaging method enables high-throughput, quantitative analysis of a large number of synapses from different brain regions. To demonstrate the capabilities of this approach, we have determined the organization of ten protein components of the presynaptic active zone and the postsynaptic density. Variations in synapse morphology, neurotransmitter receptor composition, and receptor distribution were observed both among synapses and across different brain regions. Combination with optogenetics further allowed molecular events associated with synaptic plasticity to be resolved at the single-synapse level.
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