Zhuo Yizhou, Luo Bin, Yi Xinyang, Dong Hui, Wan Jinxia, Cai Ruyi, Williams John T, Qian Tongrui, Campbell Malcolm G, Miao Xiaolei, Li Bozhi, Wei Yu, Li Guochuan, Wang Huan, Zheng Yu, Watabe-Uchida Mitsuko, Li Yulong
State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing 100871, China.
PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China.
bioRxiv. 2023 Aug 25:2023.08.24.554559. doi: 10.1101/2023.08.24.554559.
Dopamine (DA) plays multiple roles in a wide range of physiological and pathological processes via a vast network of dopaminergic projections. To fully dissect the spatiotemporal dynamics of DA release in both dense and sparsely innervated brain regions, we developed a series of green and red fluorescent GPCR activation-based DA (GRAB) sensors using a variety of DA receptor subtypes. These sensors have high sensitivity, selectivity, and signal-to-noise properties with subsecond response kinetics and the ability to detect a wide range of DA concentrations. We then used these sensors in freely moving mice to measure both optogenetically evoked and behaviorally relevant DA release while measuring neurochemical signaling in the nucleus accumbens, amygdala, and cortex. Using these sensors, we also detected spatially resolved heterogeneous cortical DA release in mice performing various behaviors. These next-generation GRAB sensors provide a robust set of tools for imaging dopaminergic activity under a variety of physiological and pathological conditions.
多巴胺(DA)通过广泛的多巴胺能投射网络在多种生理和病理过程中发挥多种作用。为了全面剖析密集和稀疏神经支配的脑区中DA释放的时空动态,我们使用多种DA受体亚型开发了一系列基于绿色和红色荧光GPCR激活的DA(GRAB)传感器。这些传感器具有高灵敏度、选择性和信噪比特性,具有亚秒级的响应动力学,并且能够检测宽范围的DA浓度。然后,我们在自由活动的小鼠中使用这些传感器来测量光遗传学诱发的和与行为相关的DA释放,同时测量伏隔核、杏仁核和皮层中的神经化学信号。使用这些传感器,我们还在执行各种行为的小鼠中检测到了空间分辨的异质性皮层DA释放。这些下一代GRAB传感器为在各种生理和病理条件下对多巴胺能活动进行成像提供了一套强大的工具。