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
-
- Electric Stimulation
- Zebrafish
- Intravital Microscopy
- Mesencephalon/metabolism*
- In Vitro Techniques
- Mice
- Hypothalamus/metabolism*
- Animals, Genetically Modified
- Microscopy, Fluorescence
- Receptors, Adrenergic, alpha-2/genetics*
- Norepinephrine/metabolism*
- Locus Coeruleus/metabolism*
- Optogenetics
- Protein Engineering
- Animals
- Green Fluorescent Proteins/genetics*
- PubMed
- 30922875 Full text @ Neuron
Citation
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. (2019) A Genetically Encoded Fluorescent Sensor for Rapid and Specific In Vivo Detection of Norepinephrine. Neuron. 102(4):745-761.e8.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping