| Title | An optimized acetylcholine sensor for monitoring in vivo cholinergic activity |
| Authors | Jing, Miao Li, Yuexuan Zeng, Jianzhi Huang, Pengcheng Skirzewski, Miguel Kljakic, Ornela Peng, Wanling Qian, Tongrui Tan, Ke Zou, Jing Trinh, Simon Wu, Runlong Zhang, Shichen Pan, Sunlei Hires, Samuel A. Xu, Min Li, Haohong Saksida, Lisa M. Prado, Vania F. Bussey, Timothy J. Prado, Marco A. M. Chen, Liangyi Cheng, Heping Li, Yulong |
| Affiliation | Chinese Inst Brain Res, Beijing, Peoples R China Peking Univ, Sch Life Sci, State Key Lab Membrane Biol, Beijing, Peoples R China PKU IDG McGovern Inst Brain Res, Beijing, Peoples R China Peking Univ, Hlth Sci Ctr, Beijing, Peoples R China Peking Univ, Acad Adv Interdisciplinary Studies, Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China Huazhong Univ Sci & Technol, Wuhan Natl Lab Optoelect, Britton Chance Ctr Biomed Photon, Wuhan, Peoples R China Huazhong Univ Sci & Technol, Sch Engn Sci, Collaborat Innovat Ctr Biomed Engn, MoE Key Lab Biomed Photon, Wuhan, Peoples R China Univ Western Ontario, BrainsCAN Rodent Cognit Core, London, ON, Canada Univ Western Ontario, Robarts Res Inst, Brain & Mind Inst, Dept Physiol & Pharmacol,Schulich Sch Med & Dent, London, ON, Canada Univ Western Ontario, Dept Anat & Cell Biol, London, ON, Canada Univ Western Ontario, Brain & Mind Inst, Dept Anat & Cell Biol, London, ON, Canada Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, State Key Lab Neurosci, Inst Neurosci, Shanghai, Peoples R China Univ Southern Calif, Sect Neurobiol, Dept Biol Sci, Los Angeles, CA 90007 USA Peking Univ, Inst Mol Med, Beijing, Peoples R China Chinese Acad Med Sci, PKU Nanjing Inst Translat Med, Res Unit Mitochondria Brain Dis, Nanjing, Peoples R China |
| Keywords | SLEEP EXCITATION RECEPTOR RELEASE SYSTEM M-1 |
| Issue Date | Sep-2020 |
| Publisher | NATURE METHODS |
| Abstract | The ability to directly measure acetylcholine (ACh) release is an essential step toward understanding its physiological function. Here we optimized the GRAB(ACh)(GPCR-activation-based ACh) sensor to achieve substantially improved sensitivity in ACh detection, as well as reduced downstream coupling to intracellular pathways. The improved version of the ACh sensor retains the subsecond response kinetics, physiologically relevant affinity and precise molecular specificity for ACh of its predecessor. Using this sensor, we revealed compartmental ACh signals in the olfactory center of transgenic flies in response to external stimuli including odor and body shock. Using fiber photometry recording and two-photon imaging, our ACh sensor also enabled sensitive detection of single-trial ACh dynamics in multiple brain regions in mice performing a variety of behaviors. A genetically encoded acetylcholine sensor with improved sensitivity allows detection of cholinergic neurotransmission in vivo in theDrosophilaand mouse brain. |
| URI | http://hdl.handle.net/20.500.11897/607751 |
| ISSN | 1548-7091 |
| DOI | 10.1038/s41592-020-0953-2 |
| Indexed | SCI(E) |
| Appears in Collections: | 生命科学学院 膜生物学国家重点实验室 医学部待认领 前沿交叉学科研究院 分子医学研究所 |
