PUBLICATION

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

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.
ID
ZDB-PUB-190405-25
Date
2018
Source
Cell   174: 481-496.e19 (Journal)
Registered Authors
Du, Jiu Lin
Keywords
GPCR, GRAB(DA), dopamine, sensor
MeSH Terms
  • Zebrafish Proteins/genetics
  • Female
  • Animals
  • Drosophila/metabolism*
  • TRPV Cation Channels/genetics
  • Neurons/cytology
  • Neurons/metabolism
  • Behavior, Animal
  • Mice
  • Microscopy, Fluorescence
  • Receptors, G-Protein-Coupled/genetics
  • Humans
  • Mice, Inbred C57BL
  • Male
  • Zebrafish/metabolism*
  • HEK293 Cells
  • Dopamine/analysis*
  • Dopamine/metabolism
  • Green Fluorescent Proteins/genetics
  • Optogenetics/methods
  • Animals, Genetically Modified/genetics
  • Animals, Genetically Modified/metabolism
(all 22)
PubMed
30007419 Full text @ Cell
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.
Genes / Markers
Figures
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Expression
Phenotype
No data available
Mutations / Transgenics
Human Disease / Model
No data available
Sequence Targeting Reagents
No data available
Fish
No data available
Antibodies
No data available
Orthology
Engineered Foreign Genes
Marker Marker Type Name
GRABDA1hEFGGRABDA1h
GRABDA1mEFGGRABDA1m
TagRFPEFGTagRFP
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Mapping