Super-Resolution Microscopy Opens New Doors to Life at the Nanoscale
Super-Resolution Microscopy Opens New Doors to Life at the Nanoscale
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DOI：
10.1523/jneurosci.1125-22.2022
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发表时间：
2022-11-09
影响因子：
5.3
通讯作者：
Willig, Katrin I.
中科院分区：
文献类型：
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作者：
Fuhrmann, Martin;Gockel, Nala;Willig, Katrin I.
超分辨率荧光显微镜在神经科学领域具有巨大的发现潜力。产生神经元独特且令人眼花缭乱的电化学活动的许多分子机制和解剖学特化都是纳米级设计的，范围在 1 nm 到 1 lm 之间。正是在这种规模上，大多数未知和令人兴奋的行动都发生了，也是细胞生物学家们梦想中的聚集地，但直到最近，它还是光学显微镜的禁区。虽然超分辨率显微镜的光学原理现已牢固确立，但该技术在许多关键领域继续快速发展，提高了其性能和可靠性，并使其更易于使用和用户友好，这是迫切需要的。事实上，超分辨率显微镜技术如今广泛用于可视化固定或活细胞中免疫标记蛋白质的分布。然而，超分辨率显微镜在神经科学领域的巨大潜力在于揭示活体组织环境中的纳米级结构和生化活动，这应该得到更充分的开发和利用。在这篇综述中，我们将展示几个基于 STED 和 RESOLFT 超分辨率显微镜的生动例子，说明体内纳米成像的可能性和挑战，以激发技术开发人员和神经生物学家的兴趣。我们将介绍促进体内应用的最新技术进展，并分享对神经元和神经胶质细胞之间细胞通信的纳米级机制的新生物学见解。
Super-resolution fluorescence microscopy holds tremendous potential for discovery in neuroscience. Much of the molecular machinery and anatomic specializations that give rise to the unique and bewildering electrochemical activity of neurons are nanoscale by design, ranging somewhere between 1 nm and 1 lm. It is at this scale where most of the unknown and exciting action is and where cell biolo-gists flock to in their dreams, but it was off limits for light microscopy until recently. While the optical principles of super-resolution microscopy are firmly established by now, the technology continues to advance rapidly in many crucial areas, enhancing its perform-ance and reliability, and making it more accessible and user-friendly, which is sorely needed. Indeed, super-resolution microscopy tech-niques are nowadays widely used for visualizing immunolabeled protein distributions in fixed or living cells. However, a great potential of super-resolution microscopy for neuroscience lies in shining light on the nanoscale structures and biochemical activities in live-tissue settings, which should be developed and harnessed much more fully. In this review, we will present several vivid examples based on STED and RESOLFT super-resolution microscopy, illustrating the possibilities and challenges of nano-imaging in vivo to pique the interest of tech-developers and neurobiologists alike. We will cover recent technical progress that is facilitating in vivo applications, and share new biological insights into the nanoscale mechanisms of cellular communication between neurons and glia.