Format

Send to

Choose Destination
Cell. 2018 Jul 12;174(2):481-496.e19. doi: 10.1016/j.cell.2018.06.042.

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

Author information

1
State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, 100871 Beijing, China; PKU-IDG/McGovern Institute for Brain Research, 100871 Beijing, China.
2
State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, 100871 Beijing, China; PKU-IDG/McGovern Institute for Brain Research, 100871 Beijing, China; Peking-Tsinghua Center for Life Sciences, 100871 Beijing, China.
3
Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
4
Gladstone Institutes, San Francisco, CA 94158, USA.
5
State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, 100871 Beijing, China.
6
Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, 200031 Shanghai, China; University of Chinese Academy of Sciences, 100049 Beijing, China.
7
Neuroscience Institute, New York University School of Medicine, New York, NY 10016, USA.
8
PKU-IDG/McGovern Institute for Brain Research, 100871 Beijing, China; Peking-Tsinghua Center for Life Sciences, 100871 Beijing, China; College of Biological Sciences, China Agricultural University, 100193 Beijing, China.
9
Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, 200031 Shanghai, China.
10
Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China.
11
Neuroscience Institute, New York University School of Medicine, New York, NY 10016, USA; Department of Psychiatry, New York University School of Medicine, New York, NY 10016, USA.
12
Gladstone Institutes, San Francisco, CA 94158, USA; Department of Neurology, Kavli Institute for Fundamental Neuroscience, Weill Institute for Neurosciences, Department of Physiology, University of California, San Francisco, CA 94158, USA.
13
State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, 100871 Beijing, China; PKU-IDG/McGovern Institute for Brain Research, 100871 Beijing, China; Peking-Tsinghua Center for Life Sciences, 100871 Beijing, China. Electronic address: yulongli@pku.edu.cn.

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 (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.

KEYWORDS:

GPCR; GRAB(DA); dopamine; sensor

PMID:
30007419
PMCID:
PMC6092020
DOI:
10.1016/j.cell.2018.06.042
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center