Improved green and red GRAB sensors for monitoring spatiotemporal serotonin release in vivo

Fei Deng; Jinxia Wan; Guochuan Li; Hui Dong; Xiju Xia; Yipan Wang; Xuelin Li; Chaowei Zhuang; Yu Zheng; Laixin Liu; Yuqi Yan; Jiesi Feng; Yulin Zhao; Hao Xie; Yulong Li

doi:10.1038/s41592-024-02188-8

Improved green and red GRAB sensors for monitoring spatiotemporal serotonin release in vivo

Nat Methods. 2024 Apr;21(4):692-702. doi: 10.1038/s41592-024-02188-8. Epub 2024 Mar 5.

Authors

Fei Deng^#^{1

2

3}, Jinxia Wan^#^{1

2}, Guochuan Li^{1

2}, Hui Dong^{1

2}, Xiju Xia^{1

2

4}, Yipan Wang^{1

2}, Xuelin Li^{1

2}, Chaowei Zhuang⁵, Yu Zheng^{1

2

6}, Laixin Liu^{1

2

6}, Yuqi Yan^{1

2

6}, Jiesi Feng^{1

2}, Yulin Zhao^{1

2}, Hao Xie⁵, Yulong Li^{7

8

9

10

11}

Affiliations

¹ State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, China.
² PKU-IDG/McGovern Institute for Brain Research, Beijing, China.
³ Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, China.
⁴ Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
⁵ Department of Automation, Tsinghua University, Beijing, China.
⁶ Peking-Tsinghua Center for Life Sciences, New Cornerstone Science Laboratory, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
⁷ State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, China. yulongli@pku.edu.cn.
⁸ PKU-IDG/McGovern Institute for Brain Research, Beijing, China. yulongli@pku.edu.cn.
⁹ Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China. yulongli@pku.edu.cn.
¹⁰ Peking-Tsinghua Center for Life Sciences, New Cornerstone Science Laboratory, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China. yulongli@pku.edu.cn.
¹¹ Chinese Institute for Brain Research, Beijing, China. yulongli@pku.edu.cn.

^# Contributed equally.

PMID: 38443508
DOI: 10.1038/s41592-024-02188-8

Abstract

The serotonergic system plays important roles in both physiological and pathological processes, and is a therapeutic target for many psychiatric disorders. Although several genetically encoded GFP-based serotonin (5-HT) sensors were recently developed, their sensitivities and spectral profiles are relatively limited. To overcome these limitations, we optimized green fluorescent G-protein-coupled receptor (GPCR)-activation-based 5-HT (GRAB_5-HT) sensors and developed a red fluorescent GRAB_5-HT sensor. These sensors exhibit excellent cell surface trafficking and high specificity, sensitivity and spatiotemporal resolution, making them suitable for monitoring 5-HT dynamics in vivo. Besides recording subcortical 5-HT release in freely moving mice, we observed both uniform and gradient 5-HT release in the mouse dorsal cortex with mesoscopic imaging. Finally, we performed dual-color imaging and observed seizure-induced waves of 5-HT release throughout the cortex following calcium and endocannabinoid waves. In summary, these 5-HT sensors can offer valuable insights regarding the serotonergic system in both health and disease.

MeSH terms

Animals
Cerebral Cortex / metabolism
Humans
Mice
Receptors, G-Protein-Coupled* / metabolism
Serotonin* / metabolism

Substances

Serotonin
Receptors, G-Protein-Coupled