A genetically encoded sensor for measuring serotonin dynamics

Serotonin (5-HT) is a phylogenetically conserved monoamine neurotransmitter modulating important processes in the brain. To directly visualize the release of 5-HT, we developed a genetically encoded G-protein-coupled receptor (GPCR)-activation-based 5-HT (GRAB 5-HT ) sensor with high sensitivity, hi...

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Bibliographic Details
Published in:Nature neuroscience Vol. 24; no. 5; pp. 746 - 752
Main Authors: Wan, Jinxia, Peng, Wanling, Li, Xuelin, Qian, Tongrui, Song, Kun, Zeng, Jianzhi, Deng, Fei, Hao, Suyu, Feng, Jiesi, Zhang, Peng, Zhang, Yajun, Zou, Jing, Pan, Sunlei, Shin, Mimi, Venton, B. Jill, Zhu, J. Julius, Jing, Miao, Xu, Min, Li, Yulong
Format: Journal Article
Language:English
Published: New York Nature Publishing Group US 01.05.2021
Nature Publishing Group
Subjects:
631/1647/1888
631/378
631/443
96/35
Animal Genetics and Genomics
Animals
Behavioral Sciences
Biological Techniques
Biomedical and Life Sciences
Biomedicine
Biosensors
Brain research
Female
G protein-coupled receptors
Genetic code
Genetic engineering
Health aspects
HEK293 Cells
Humans
Male
Methods
Mice
Molecular dynamics
Monoamines
Neurobiology
Neurons - metabolism
Neurosciences
Neurotransmitters
Phylogeny
Physiological aspects
Rats
Receptors, G-Protein-Coupled - metabolism
Selectivity
Sensitivity
Sensors
Serotonergic Neurons - metabolism
Serotonin
Serotonin - metabolism
Signal Transduction - physiology
technical-report
China
ISSN:1097-6256, 1546-1726, 1546-1726
Online Access:Get full text
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Description
Summary:Serotonin (5-HT) is a phylogenetically conserved monoamine neurotransmitter modulating important processes in the brain. To directly visualize the release of 5-HT, we developed a genetically encoded G-protein-coupled receptor (GPCR)-activation-based 5-HT (GRAB 5-HT ) sensor with high sensitivity, high selectivity, subsecond kinetics and subcellular resolution. GRAB 5-HT detects 5-HT release in multiple physiological and pathological conditions in both flies and mice and provides new insights into the dynamics and mechanisms of 5-HT signaling. The authors develop a genetically encoded GPCR-based sensor to image serotonin dynamics in behaving animals with high specificity, sensitivity and spatiotemporal resolution.
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Y.L. conceived and supervised the project. J.W., M.J., F.D., S.H., J.F., J. Zou, and S.P. performed the experiments related to developing, optimizing, and characterizing the sensor in cultured HEK293T cells and neurons. T.Q. performed the experiments using AAVs in slices. P.Z., Y.Z. and M.S. performed the simultaneous imaging and FSCV experiments using Sindbis virus in slices under the supervision of J.J.Z and B.J.V. X.L. and J. Zeng performed the Drosophila experiments. W.P. and K.S. performed the fiber-photometry recordings in behaving mice under the supervision of M.X. J.W. performed the two-photon imaging in head-fixed mice. All authors contributed to the data interpretation and analysis. Y.L. and J.W. wrote the manuscript with input from all other authors.
Author contributions
ISSN:1097-6256
1546-1726
1546-1726
DOI:10.1038/s41593-021-00823-7