以色列魏茨曼科学研究所Ofer Yizhar等研究人员合作发现，一种双稳态抑制性optoGPCR可用于神经回路多重光遗传控制。相关论文于2024年5月29日在线发表在《自然—方法学》杂志上。

研究人员系统地评估了用于光遗传学应用的多种双稳态视蛋白，并发现Platynereis dumerilii纤毛视蛋白（PdCO）是一种高效、多用途的光激活双稳态G蛋白偶联受体，可以在体内高时间精度地抑制哺乳动物神经元的突触传递。PdCO具有有用的生物物理特性，可与其他光遗传致动器和报告器进行光谱复用。研究人员证明，PdCO可用于在行动动物的长程投射中进行可逆的功能缺失实验，从而实现详细的突触特异性功能回路图谱。

研究人员表示，信息通过长程轴突释放的神经递质在脑区之间传递。要了解这种远距离连接的活动如何对行为产生影响，就需要采用有效的方法来可逆地操纵它们的功能。化学遗传学和光遗传学工具通过内源性G蛋白偶联受体通路发挥作用，可用于调节突触传递，但现有工具在灵敏度、时空精度或光谱复用能力方面存在局限。

附：英文原文

Title: A bistable inhibitory optoGPCR for multiplexed optogenetic control of neural circuits

Author: Wietek, Jonas, Nozownik, Adrianna, Pulin, Mauro, Saraf-Sinik, Inbar, Matosevich, Noa, Gowrishankar, Raajaram, Gat, Asaf, Malan, Daniela, Brown, Bobbie J., Dine, Julien, Imambocus, Bibi Nusreen, Levy, Rivka, Sauter, Kathrin, Litvin, Anna, Regev, Noa, Subramaniam, Suraj, Abrera, Khalid, Summarli, Dustin, Goren, Eva Madeline, Mizrachi, Gili, Bitton, Eyal, Benjamin, Asaf, Copits, Bryan A., Sasse, Philipp, Rost, Benjamin R., Schmitz, Dietmar, Bruchas, Michael R., Soba, Peter, Oren-Suissa, Meital, Nir, Yuval, Wiegert, J. Simon, Yizhar, Ofer

Issue&Volume: 2024-05-29

Abstract: Information is transmitted between brain regions through the release of neurotransmitters from long-range projecting axons. Understanding how the activity of such long-range connections contributes to behavior requires efficient methods for reversibly manipulating their function. Chemogenetic and optogenetic tools, acting through endogenous G-protein-coupled receptor pathways, can be used to modulate synaptic transmission, but existing tools are limited in sensitivity, spatiotemporal precision or spectral multiplexing capabilities. Here we systematically evaluated multiple bistable opsins for optogenetic applications and found that the Platynereis dumerilii ciliary opsin (PdCO) is an efficient, versatile, light-activated bistable G-protein-coupled receptor that can suppress synaptic transmission in mammalian neurons with high temporal precision in vivo. PdCO has useful biophysical properties that enable spectral multiplexing with other optogenetic actuators and reporters. We demonstrate that PdCO can be used to conduct reversible loss-of-function experiments in long-range projections of behaving animals, thereby enabling detailed synapse-specific functional circuit mapping.

DOI: 10.1038/s41592-024-02285-8

Source: https://www.nature.com/articles/s41592-024-02285-8