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Cited by 837Advanced Fluorescence Microscopy TechniquesNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

A Genetically Encoded Fluorescent Sensor Enables Rapid and Specific Detection of Dopamine in Flies, Fish, and Mice

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Sun, Fangmiao, Zeng, Jianzhi, Jing, Miao, Zhou, Jingheng, Feng, Jiesi, Owen, Scott F., Luo, Yichen, Li, Funing +13 more·2018·Cell
DOI 10.1016/j.cell.2018.06.042PMC PMC6092020

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Abstract

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 (GRAB DA) sensors that enable these measurements. In response to extracellular DA, GRAB DA sensors exhibit large fluorescence increases (ΔF/F 0 ∼90%) with subcellular resolution, subsecond kinetics, nanomolar to submicromolar affinities, and excellent molecular specificity. GRAB DA 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, GRAB DA sensors readily report optogenetically elicited nigrostriatal DA release and depict dynamic mesoaccumbens DA signaling during Pavlovian conditioning or during sexual behaviors. Thus, GRAB DA sensors enable spatiotemporally precise measurements of DA dynamics in a variety of model organisms while exhibiting complex behaviors.

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Authors
Sun, F., Zeng, J., Jing, M., Zhou, J., Feng, J., Owen, S. F., Luo, Y., Li, F., Wang, H., Yamaguchi, T., Yong, Z., Gao, Y., Peng, W., Wang, L., Zhang, S., Du, J., Lin, D., Xu, M., Kreitzer, A. C., Cui, G., & Li, Y.
Affiliations
  • Peking University (CN)
  • National Institute of Environmental Health Sciences (US)
  • Gladstone Institutes (US)
  • Chinese Academy of Sciences (CN)
  • New York University (US)
  • Shanghai Jiao Tong University (CN)
  • NYU Langone Health (US)
Corresponding author
Li, Yulong
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2018-07
Volume
174
Issue
2
Pages
481-496.e19
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2018.06.042
PMC
PMC6092020
OpenAlex
W2807128224
Cited by
837
References
6
Citations by year
2026: 91 · 2025: 109 · 2024: 107 · 2023: 119 · 2022: 120 · 2021: 110 · 2020: 99 · 2019: 71 · 2018: 11
FWCI
37.37
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Basic Research Program of China (2015CB856402)
  • General Program of National Natural Science Foundation of China (31671118)
  • NIH BRAIN Initiative (NS103558)
  • Junior Thousand Talents Program of China
  • Peking-Tsinghua Center for Life Sciences
  • State Key Laboratory of Membrane Biology at Peking University School of Life Sciences
  • NIH (F32 NS083369, K99 MH110597, R01MH101377, R21HD090563)
  • Ministry of Science and Technology of the People's Republic of China (2017YFA0505700)
  • Uehara postdoctoral fellowship
  • Irma T. Hirschl Career Scientist Award
  • Intramural Research Program of the NIH/NIEHS of the United States (1ZIAES103310)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
dopamine detection, genetically encoded fluorescent sensors, GPCR activation, dopamine release, optogenetic stimulation, nigrostriatal pathway, classical conditioning, sexual behavior, freely moving mice, Drosophila, zebrafish, brain slices, neurotransmitter dynamics
MeSH terms
Animals, Behavior, Animal, Dopamine, Drosophila, Female, Humans, Male, Mice, Inbred C57BL, Microscopy, Fluorescence, Neurons, Zebrafish, Zebrafish Proteins, Animals, Genetically Modified, Receptors, G-Protein-Coupled, Green Fluorescent Proteins, TRPV Cation Channels, Mice, HEK293 Cells, Optogenetics

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