A Genetically Encoded Fluorescent Sensor for Rapid and Specific In Vivo Detection of Norepinephrine

Neuron. 2019 May 22;102(4):745-761.e8. doi: 10.1016/j.neuron.2019.02.037. Epub 2019 Mar 25.


Norepinephrine (NE) is a key biogenic monoamine neurotransmitter involved in a wide range of physiological processes. However, its precise dynamics and regulation remain poorly characterized, in part due to limitations of available techniques for measuring NE in vivo. Here, we developed a family of GPCR activation-based NE (GRABNE) sensors with a 230% peak ΔF/F0 response to NE, good photostability, nanomolar-to-micromolar sensitivities, sub-second kinetics, and high specificity. Viral- or transgenic-mediated expression of GRABNE sensors was able to detect electrical-stimulation-evoked NE release in the locus coeruleus (LC) of mouse brain slices, looming-evoked NE release in the midbrain of live zebrafish, as well as optogenetically and behaviorally triggered NE release in the LC and hypothalamus of freely moving mice. Thus, GRABNE sensors are robust tools for rapid and specific monitoring of in vivo NE transmission in both physiological and pathological processes.

Keywords: GPCR; GRABNE; neurotransmitter; norepinephrine; sensor.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Electric Stimulation
  • Green Fluorescent Proteins / genetics*
  • Hypothalamus / metabolism*
  • In Vitro Techniques
  • Intravital Microscopy
  • Locus Coeruleus / metabolism*
  • Mesencephalon / metabolism*
  • Mice
  • Microscopy, Fluorescence
  • Norepinephrine / metabolism*
  • Optogenetics
  • Protein Engineering
  • Receptors, Adrenergic, alpha-2 / genetics*
  • Zebrafish


  • Receptors, Adrenergic, alpha-2
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Norepinephrine