Division of Molecular and Cellular Pharmacology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
Division of Membrane Physiology, Department of Molecular and Cellular Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Aichi 444-8787, Japan.
J Neurosci. 2024 Jun 5;44(23):e2104232024. doi: 10.1523/JNEUROSCI.2104-23.2024.
A decade ago, in 2013, and over the course of 4 summer months, three separate observations were reported that each shed light independently on a new molecular organization that fundamentally reshaped our perception of excitatory synaptic transmission (Fukata et al., 2013; MacGillavry et al., 2013; Nair et al., 2013). This discovery unveiled an intricate arrangement of AMPA-type glutamate receptors and their principal scaffolding protein PSD-95, at synapses. This breakthrough was made possible, thanks to advanced super-resolution imaging techniques. It fundamentally changed our understanding of excitatory synaptic architecture and paved the way for a brand-new area of research. In this Progressions article, the primary investigators of the nanoscale organization of synapses have come together to chronicle the tale of their discovery. We recount the initial inquiry that prompted our research, the preceding studies that inspired our work, the technical obstacles that were encountered, and the breakthroughs that were made in the subsequent decade in the realm of nanoscale synaptic transmission. We review the new discoveries made possible by the democratization of super-resolution imaging techniques in the field of excitatory synaptic physiology and architecture, first by the extension to other glutamate receptors and to presynaptic proteins and then by the notion of trans-synaptic organization. After describing the organizational modifications occurring in various pathologies, we discuss briefly the latest technical developments made possible by super-resolution imaging and emerging concepts in synaptic physiology.
十年前，也就是 2013 年，在四个夏季的时间里，有三项独立的观察结果分别报道，这三项观察结果独立地揭示了一种新的分子组织，从根本上改变了我们对兴奋性突触传递的认识（Fukata 等人，2013；MacGillavry 等人，2013；Nair 等人，2013）。这一发现揭示了在突触处 AMPA 型谷氨酸受体及其主要支架蛋白 PSD-95 的复杂排列。这一突破得益于先进的超分辨率成像技术。它从根本上改变了我们对兴奋性突触结构的理解，为一个全新的研究领域铺平了道路。在这篇进展文章中，突触纳米结构的主要研究人员齐聚一堂，讲述了他们发现的故事。我们叙述了促使我们进行研究的最初探究，启发我们工作的前期研究，遇到的技术障碍，以及在随后的十年中在纳米级突触传递领域取得的突破。我们回顾了超分辨率成像技术在兴奋性突触生理学和结构领域普及所带来的新发现，首先是扩展到其他谷氨酸受体和突触前蛋白，然后是跨突触组织的概念。在描述了各种病变中发生的组织变化之后，我们简要讨论了超分辨率成像和突触生理学中新兴概念所带来的最新技术发展。
