CoChat
Sign Up
Cited by 302Advanced Fluorescence Microscopy TechniquesNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

A genetically encoded sensor for measuring serotonin dynamics

Open access
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·2021·Nature Neuroscience
DOI 10.1038/s41593-021-00823-7PMC PMC8544647

Published version of a preprint

Open this paper in CoChat — free accountOpen PDF

Abstract

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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41593-021-00823-7

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Flow fiber photometry enables recordings from deep brain tissues and combined monitoring of blood and CSF dynamics using virally-delivered biosensors.

    “flow fiber photometry enables recordings from deep brain tissues and combined monitoring of blood and CSF dynamics using virally-delivered biosensors45,101–104.”

    From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [102]

    The Methods section, “Fiber-photometry recording in mice” (page unavailable), describes optical-fiber recordings from mouse brain regions using AAV-delivered serotonin sensors. The paper supports that part of the sentence, but our copy does not describe combined monitoring of blood and CSF dynamics. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 34

  1. Lesch, K. P. et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 1527–1531 (1996). · DOI · Paper page
  2. Li, Y. et al. Serotonin neurons in the dorsal raphe nucleus encode reward signals. Nat. Commun. 7, 10503 (2016). · DOI
  3. Portas, C. M. et al. On-line detection of extracellular levels of serotonin in dorsal raphe nucleus and frontal cortex over the sleep/wake cycle in the freely moving rat. Neuroscience 83, 807–814 (1998). · DOI
  4. Fuller, R. W. Uptake inhibitors increase extracellular serotonin concentration measured by brain microdialysis. Life Sci. 55, 163–167 (1994). · DOI
  5. Bunin, M. A., Prioleau, C., Mailman, R. B. & Wightman, R. M. Release and uptake rates of 5-hydroxytryptamine in the dorsal raphe and substantia nigra reticulata of the rat brain. J. Neurochem. 70, 1077–1087 (1998). · DOI
  6. Candelario, J. & Chachisvilis, M. Mechanical stress stimulates conformational changes in 5-hydroxytryptamine receptor 1B in bone cells. Cell. Mol. Bioeng. 5, 277–286 (2012). · DOI
  7. Jing, M. et al. A genetically encoded fluorescent acetylcholine indicator for in vitro and in vivo studies. Nat. Biotechnol. 36, 726–737 (2018). · DOI
  8. Patriarchi, T. et al. Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors. Science 360, eaat4422 (2018). · DOI
  9. Sun, F. et al. A genetically encoded fluorescent sensor enables rapid and specific detection of dopamine in flies, fish, and mice. Cell 174, 481–496 (2018). · DOI · Paper page
  10. Feng, J. et al. A genetically encoded fluorescent sensor for rapid and specific in vivo detection of norepinephrine. Neuron 102, 745–761 (2019). · DOI · Paper page
  11. Bajar, B. T. et al. Improving brightness and photostability of green and red fluorescent proteins for live cell imaging and FRET reporting. Sci. Rep. 6, 20889 (2016). · DOI
  12. Pedelacq, J. D., Cabantous, S., Tran, T., Terwilliger, T. C. & Waldo, G. S. Engineering and characterization of a superfolder green fluorescent protein. Nat. Biotechnol. 24, 79–88 (2006). · DOI
  13. Peng, Y. et al. 5-HT2C receptor structures reveal the structural basis of GPCR polypharmacology. Cell 172, 719–730 (2018). · DOI
  14. Ballesteros, J. A. & Weinstein, H. [19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors. Methods in Neurosciences 25, 366–428 (1995). · DOI
  15. Harada, K. et al. Red fluorescent protein-based cAMP indicator applicable to optogenetics and in vivo imaging. Sci. Rep. 7, 7351 (2017). · DOI
  16. Wan, Q. et al. Mini G protein probes for active G protein-coupled receptors (GPCRs) in live cells. J. Biol. Chem. 293, 7466–7473 (2018). · DOI
  17. Barnea, G. et al. The genetic design of signaling cascades to record receptor activation. Proc. Natl Acad. Sci. USA 105, 64–69 (2008). · DOI
  18. Ishimura, K. et al. Quantitative analysis of the distribution of serotonin-immunoreactive cell bodies in the mouse brain. Neurosci. Lett. 91, 265–270 (1988). · DOI · Paper page
  19. Lee, P. T. et al. Serotonin–mushroom body circuit modulating the formation of anesthesia-resistant memory in Drosophila. Proc. Natl Acad. Sci. USA 108, 13794–13799 (2011). · DOI
  20. Keene, A. C. et al. Diverse odor-conditioned memories require uniquely timed dorsal paired medial neuron output. Neuron 44, 521–533 (2004). · DOI
  21. Yu, D. et al. Drosophila DPM neurons form a delayed and branch-specific memory trace after olfactory classical conditioning. Cell 123, 945–957 (2005). · DOI
  22. Xu, M. et al. Basal forebrain circuit for sleep–wake control. Nat. Neurosci. 18, 1641–1647 (2015). · DOI · Paper page
  23. Oikonomou, G. et al. The serotonergic raphe promote sleep in zebrafish and mice. Neuron 103, 686–701 (2019). · DOI
  24. Rudnick, G. & Wall, S. C. The molecular mechanism of ‘ecstasy’ [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Proc. Natl Acad. Sci. USA 89, 1817–1821 (1992). · DOI
  25. Bicks, L. K., Koike, H., Akbarian, S. & Morishita, H. Prefrontal cortex and social cognition in mouse and man. Front. Psychol. 6, 1805 (2015). · DOI
  26. Hagino, Y. et al. Effects of MDMA on extracellular dopamine and serotonin levels in mice lacking dopamine and/or serotonin transporters. Curr. Neuropharmacol. 9, 91–95 (2011). · DOI
  27. Wang, Q., Shui, B., Kotlikoff, M. I. & Sondermann, H. Structural basis for calcium sensing by GCaMP2. Structure 16, 1817–1827 (2008). · DOI
  28. Kroeze, W. K. et al. PRESTO-Tango as an open-source resource for interrogation of the druggable human GPCRome. Nat. Struct. Mol. Biol. 22, 362–369 (2015). · DOI · Paper page
  29. Pfeiffer, B. D., Truman, J. W. & Rubin, G. M. Using translational enhancers to increase transgene expression in Drosophila. Proc. Natl Acad. Sci. USA 109, 6626–6631 (2012). · DOI
  30. Dana, H. et al. Sensitive red protein calcium indicators for imaging neural activity. eLife 5, e12727 (2016). · DOI
  31. Gibson, D. G. et al. Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat. Methods 6, 343–345 (2009). · DOI
  32. Yusa, K. et al. Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells. Nature 478, 391–394 (2011). · DOI
  33. Shin, M. & Venton, B. J. Electrochemical measurements of acetylcholine-stimulated dopamine release in adult Drosophila melanogaster brains. Anal. Chem. 90, 10318–10325 (2018). · DOI
  34. Cantu, D. A. et al. EZcalcium: open-source toolbox for analysis of calcium imaging data. Front. Neural Circuits 14, 25 (2020). · DOI

Cited by

Sorted by citations

Metadata

Authors
Wan, J., Peng, W., Li, X., Qian, T., Song, K., Zeng, J., Deng, F., Hao, S., Feng, J., Zhang, P., Zhang, Y., Zou, J., Pan, S., Shin, M., Venton, B. J., Zhu, J. J., Jing, M., Xu, M., & Li, Y.
Affiliations
  • Peking University (CN)
  • Chinese Academy of Sciences (CN)
  • University of Virginia (US)
  • University of Southern California (US)
  • Chinese Institute for Brain Research (CN)
Corresponding author
Li, Yulong
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2021-04-05
Volume
24
Issue
5
Pages
746-752
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/s41593-021-00823-7
PMC
PMC8544647
OpenAlex
W3146171909
Cited by
302
References
6
Citations by year
2026: 30 · 2025: 61 · 2024: 58 · 2023: 55 · 2022: 59 · 2021: 28
FWCI
21.17
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Neuroscience (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Alzheimer's Association
  • National Natural Science Foundation of China (2018SHZDZX05, 31871087, 31671118, 31925017, 2018B030332001)
  • Peking University
  • State Key Laboratory of Membrane Biology
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS104670, R01NS091452, U01NS103558, R01NS051241)
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 › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
serotonin, genetically encoded biosensors, G protein-coupled receptors, neurotransmitter release, serotonin signaling, live imaging, Drosophila, mice
MeSH terms
Animals, Female, Humans, Male, Neurons, Serotonin, Signal Transduction, Receptors, G-Protein-Coupled, Mice, Rats, HEK293 Cells, Serotonergic Neurons

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 ›

Are you an author, or do you see a problem with this page? Request a review