生物
单胺类神经递质
多巴胺
神经科学
神经递质
内生
细胞生物学
刺激(心理学)
生物化学
中枢神经系统
受体
血清素
心理学
心理治疗师
作者
Fangmiao Sun,Jianzhi Zeng,Miao Jing,Jingheng Zhou,Jiguang Feng,Scott F. Owen,Yichen Luo,Funing Li,Huan Wang,Takashi Yamaguchi,Zi-hao Yong,Yijing Gao,Wanling Peng,Lizhao Wang,Siyu Zhang,Jiulin Du,Dayu Lin,Min Xu,Anatol C. Kreitzer,Guohong Cui,Yulong Li
出处
期刊:Cell
[Elsevier]
日期:2018-07-01
卷期号:174 (2): 481-496.e19
被引量:610
标识
DOI:10.1016/j.cell.2018.06.042
摘要
Dopamine (DA) is a central monoamine neurotransmitter involved in many physiological and pathological processes. A longstanding yet largely unmet goal is to measure DA changes reliably and specifically with high spatiotemporal precision, particularly in animals executing complex behaviors. Here, we report the development of genetically encoded GPCR-activation-based-DA (GRABDA) sensors that enable these measurements. In response to extracellular DA, GRABDA sensors exhibit large fluorescence increases (ΔF/F0 ∼90%) with subcellular resolution, subsecond kinetics, nanomolar to submicromolar affinities, and excellent molecular specificity. GRABDA sensors can resolve a single-electrical-stimulus-evoked DA release in mouse brain slices and detect endogenous DA release in living flies, fish, and mice. In freely behaving mice, GRABDA sensors readily report optogenetically elicited nigrostriatal DA release and depict dynamic mesoaccumbens DA signaling during Pavlovian conditioning or during sexual behaviors. Thus, GRABDA sensors enable spatiotemporally precise measurements of DA dynamics in a variety of model organisms while exhibiting complex behaviors.
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