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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified / genetics
  • Animals, Genetically Modified / metabolism
  • Behavior, Animal
  • Dopamine / analysis*
  • Dopamine / metabolism
  • Drosophila / metabolism*
  • Female
  • Green Fluorescent Proteins / genetics
  • HEK293 Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Neurons / cytology
  • Neurons / metabolism
  • Optogenetics / methods
  • Receptors, G-Protein-Coupled / genetics
  • TRPV Cation Channels / genetics
  • Zebrafish / metabolism*
  • Zebrafish Proteins / genetics


  • Receptors, G-Protein-Coupled
  • TRPV Cation Channels
  • TRPV1 protein, zebrafish
  • Zebrafish Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Dopamine