用设计的远红多巴胺传感器进行动态神经化学网络的体内多重成像

IF 45.8 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-06-05 DOI:10.1126/science.adt7705

Yu Zheng, Ruyi Cai, Kui Wang, Junwei Zhang, Yizhou Zhuo, Hui Dong, Yuqi Zhang, Yifan Wang, Fei Deng, En Ji, Yiwen Cui, Shilin Fang, Xinxin Zhang, Haiyun Huang, Kecheng Zhang, Jinxu Wang, Guochuan Li, Xiaolei Miao, Zhenghua Wang, Yuqing Yang, Shaochuang Li, Jonathan B. Grimm, Kai Johnsson, Eric R. Schreiter, Luke D. Lavis, Zhixing Chen, Yu Mu, Yulong Li

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引用次数: 0

摘要

多巴胺（DA）通过与其他神经调节剂和细胞内信号通路的复杂相互作用，在多种脑功能中起着至关重要的作用。然而，对这些复杂网络的研究一直受到同时检测体内多种神经化学物质的挑战的阻碍。为了克服这一限制，我们开发了一种单蛋白化学DA传感器HaloDA1.0，它结合了cphalotag -化学染料方法和基于G蛋白偶联受体激活（GRAB）的策略，为DA提供了高灵敏度、亚秒级响应动力学和远红到近红外光谱范围。当HaloDA1.0与现有的绿色和红色荧光神经调节剂传感器、钙指示剂、环腺苷5 ' -单磷酸传感器和光遗传学工具一起使用时，HaloDA1.0在培养神经元、脑切片和行为动物的多重成像中显示出高度的通通性，有助于深入研究动态神经化学网络。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

In vivo multiplex imaging of dynamic neurochemical networks with designed far-red dopamine sensors

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In vivo multiplex imaging of dynamic neurochemical networks with designed far-red dopamine sensors

Dopamine (DA) plays a crucial role in a variety of brain functions through intricate interactions with other neuromodulators and intracellular signaling pathways. However, studying these complex networks has been hindered by the challenge of detecting multiple neurochemicals in vivo simultaneously. To overcome this limitation, we developed a single-protein chemigenetic DA sensor, HaloDA1.0, which combines a cpHaloTag–chemical dye approach with the G protein–coupled receptor activation–based (GRAB) strategy, providing high sensitivity for DA, subsecond response kinetics, and a far-red to near-infrared spectral range. When used together with existing green and red fluorescent neuromodulator sensors, calcium indicators, cyclic adenosine 5′-monophosphate sensors, and optogenetic tools, HaloDA1.0 showed high versatility for multiplex imaging in cultured neurons, brain slices, and behaving animals, facilitating in-depth studies of dynamic neurochemical networks.

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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