PUBLICATION

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

Authors
Feng, J., Zhang, C., Lischinsky, J.E., Jing, M., Zhou, J., Wang, H., Zhang, Y., Dong, A., Wu, Z., Wu, H., Chen, W., Zhang, P., Zou, J., Hires, S.A., Zhu, J.J., Cui, G., Lin, D., Du, J., Li, Y.
ID
ZDB-PUB-190330-2
Date
2019
Source
Neuron   102(4): 745-761.e8 (Journal)
Registered Authors
Du, Jiu Lin
Keywords
GPCR, GRABNE, neurotransmitter, norepinephrine, sensor
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
PubMed
30922875 Full text @ Neuron
Abstract
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping