A genetically encoded fluorescent sensor for rapid and specific in vivo detection of norepinephrine
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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 (GRAB NE) sensors with a 230% peak ΔF/F 0 response to NE, good photostability, nanomolar-to-micromolar sensitivities, sub-second kinetics, and high specificity. Viral- or transgenic-mediated expression of GRAB NE 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, GRAB NE sensors are robust tools for rapid and specific monitoring of in vivo NE transmission in both physiological and pathological processes.
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A GRABNE probe based on an α2 adrenergic receptor has been developed for in vivo and in vitro measurement of epinephrine or norepinephrine dynamics.
“A G protein-coupled receptor (GPCR) activation-based NE (GRABNE) probe, based on an α2 adrenergic receptor, has been developed for in vivo and in vitro measurement of epinephrine or norepinephrine dynamics (Feng et al., 2019).”
From Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells (2021) · cites this paper as Feng et al., 2019
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Self-citation
- 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.
- Affiliations
- Peking University (CN)
- Chinese Academy of Sciences (CN)
- New York University (US)
- National Institutes of Health (US)
- University of Virginia (US)
- University of Southern California (US)
- Ningbo University (CN)
- NYU Langone Health (US)
- Corresponding author
- Li, Yulong
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 102
- Issue
- 4
- Pages
- 745-761.e8
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC6533151
- OpenAlex
- W2950615496
- Cited by
- 545
- References
- 74
- Citations by year
- 2026: 48 · 2025: 85 · 2024: 68 · 2023: 113 · 2022: 85 · 2021: 61 · 2020: 61 · 2019: 24
- FWCI
- 27.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- National Basic Research Program of China (2015CB856402)
- National Natural Science Foundation of China (31671118)
- NIH (U01NS103558, R01MH101377, R21HD090563)
- Junior Thousand Talents Program of China
- Peking-Tsinghua Center for Life Sciences
- State Key Laboratory of Membrane Biology at Peking University School of Life Sciences (QYZDY-SSW-SMC028)
- Chinese Academy of Sciences
- Shanghai Science and Technology Committee (18JC1410100)
- Irma T. Hirschl Career Scientist Award
- NIEHS
- Peking University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- norepinephrine, genetically encoded fluorescent sensors, GPCR activation, locus coeruleus, midbrain, hypothalamus, optogenetic stimulation, biogenic monoamines
- MeSH terms
- Intravital Microscopy, Animals, Electric Stimulation, Hypothalamus, Locus Coeruleus, Mesencephalon, Microscopy, Fluorescence, Norepinephrine, Zebrafish, Protein Engineering, Receptors, Adrenergic, alpha-2, Animals, Genetically Modified, Green Fluorescent Proteins, Mice, Optogenetics, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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