A genetically encoded fluorescent sensor for rapid and specific in vivo detection of norepinephrine
A genetically encoded fluorescent sensor for rapid and specific in vivo detection of norepinephrine
Abstract Norepinephrine (NE) and epinephrine (Epi), two key biogenic monoamine neurotransmitters, are involved in a wide range of physiological processes. However, their precise dynamics and regulation remain poorly characterized, in part due to limitations of available techniques for measuring these molecules in vivo. Here, we developed a family of GPCR Activation-Based NE/Epi (GRABNE) sensors with a 230% peak ΔF/F0 response to NE, good photostability, nanomolar-to-micromolar sensitivities, sub-second rapid kinetics, high specificity to NE vs. dopamine. Viral- or transgenic- mediated expression of GRABNE sensors were 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, GRABNE sensors are a robust tool for rapid and specific monitoring of in vivo NE/Epi transmission in both physiological and pathological processes.
Feng Jiesi、Jing Miao、Wang Huan、Zhang Yajun、Dong Ao、Wu Hao、Zou Jing、Julius Zhu J.、Lin Dayu、Zhang Peng、Li Yulong、Cui Guohong、Lischinsky Julieta、Zhou Jingheng、Chen Weiyu、Wu Zhaofa、Andrew Hires S.、Du Jiulin、Zhang Changmei
State Key Laboratory of Membrane Biology, Peking University School of Life Sciences||PKU-IDG/McGovern Institute for Brain Research||Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking UniversityState Key Laboratory of Membrane Biology, Peking University School of Life Sciences||PKU-IDG/McGovern Institute for Brain Research||Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking UniversityState Key Laboratory of Membrane Biology, Peking University School of Life Sciences||PKU-IDG/McGovern Institute for Brain ResearchState Key Laboratory of Membrane Biology, Peking University School of Life Sciences||Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University||Department of Pharmacology, University of Virginia School of MedicineState Key Laboratory of Membrane Biology, Peking University School of Life Sciences||PKU-IDG/McGovern Institute for Brain Research||Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking UniversityState Key Laboratory of Membrane Biology, Peking University School of Life Sciences||PKU-IDG/McGovern Institute for Brain Research||School of Life Sciences, Tsinghua UniversityDepartment of Biological Sciences, Neurobiology Section, University of Southern CaliforniaDepartment of Pharmacology, University of Virginia School of Medicine||School of Medicine, Ningbo University||Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen||Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyNeuroscience Institute, New York University School of Medicine||Department of Psychiatry, New York University School of Medicine||Center for Neural Science, New York UniversityDepartment of Pharmacology, University of Virginia School of MedicineState Key Laboratory of Membrane Biology, Peking University School of Life Sciences||PKU-IDG/McGovern Institute for Brain Research||Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University||Lead contactNeurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle ParkNeuroscience Institute, New York University School of Medicine||Department of Psychiatry, New York University School of Medicine||Center for Neural Science, New York UniversityNeurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle ParkInstitute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences||University of Chinese Academy of SciencesState Key Laboratory of Membrane Biology, Peking University School of Life Sciences||PKU-IDG/McGovern Institute for Brain ResearchDepartment of Biological Sciences, Neurobiology Section, University of Southern CaliforniaInstitute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences||University of Chinese Academy of SciencesInstitute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences||University of Chinese Academy of Sciences
基础医学生物科学研究方法、生物科学研究技术生理学
Feng Jiesi,Jing Miao,Wang Huan,Zhang Yajun,Dong Ao,Wu Hao,Zou Jing,Julius Zhu J.,Lin Dayu,Zhang Peng,Li Yulong,Cui Guohong,Lischinsky Julieta,Zhou Jingheng,Chen Weiyu,Wu Zhaofa,Andrew Hires S.,Du Jiulin,Zhang Changmei.A genetically encoded fluorescent sensor for rapid and specific in vivo detection of norepinephrine[EB/OL].(2025-03-28)[2025-05-01].https://www.biorxiv.org/content/10.1101/449546.点此复制
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