An optimized acetylcholine sensor for monitoring in vivo cholinergic activity.

Autor: Jing M; Chinese Institute for Brain Research, Beijing, China. jingmiao@cibr.ac.cn., Li Y; State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China.; PKU-IDG/McGovern Institute for Brain Research, Beijing, China.; Peking University Health Science Center, Beijing, China., Zeng J; State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China.; PKU-IDG/McGovern Institute for Brain Research, Beijing, China.; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China., Huang P; Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics; MoE Key Laboratory for Biomedical Photonics, Collaborative Innovation Center for Biomedical Engineering, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, China., Skirzewski M; BrainsCAN Rodent Cognition Core, The University of Western Ontario, London, Ontario, Canada., Kljakic O; Robarts Research Institute, Department of Physiology and Pharmacology, Schulich School of Medecine and Dentistry, Brain and Mind Institute, The University of Western Ontario, London, Ontario, Canada.; Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario, Canada.; Department of Anatomy and Cell Biology, Brain and Mind Institute, The University of Western Ontario, London, Ontario, Canada., Peng W; Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China., Qian T; State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China.; PKU-IDG/McGovern Institute for Brain Research, Beijing, China.; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China., Tan K; State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China.; PKU-IDG/McGovern Institute for Brain Research, Beijing, China., Zou J; Department of Biological Sciences, Section of Neurobiology, University of Southern California, Los Angeles, CA, USA., Trinh S; Department of Biological Sciences, Section of Neurobiology, University of Southern California, Los Angeles, CA, USA., Wu R; Institute of Molecular Medicine, Peking University, Beijing, China., Zhang S; State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China.; PKU-IDG/McGovern Institute for Brain Research, Beijing, China., Pan S; State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China.; PKU-IDG/McGovern Institute for Brain Research, Beijing, China.; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China., Hires SA; Department of Biological Sciences, Section of Neurobiology, University of Southern California, Los Angeles, CA, USA., Xu M; Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China., Li H; Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics; MoE Key Laboratory for Biomedical Photonics, Collaborative Innovation Center for Biomedical Engineering, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, China., Saksida LM; Robarts Research Institute, Department of Physiology and Pharmacology, Schulich School of Medecine and Dentistry, Brain and Mind Institute, The University of Western Ontario, London, Ontario, Canada., Prado VF; Robarts Research Institute, Department of Physiology and Pharmacology, Schulich School of Medecine and Dentistry, Brain and Mind Institute, The University of Western Ontario, London, Ontario, Canada.; Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario, Canada.; Department of Anatomy and Cell Biology, Brain and Mind Institute, The University of Western Ontario, London, Ontario, Canada., Bussey TJ; Robarts Research Institute, Department of Physiology and Pharmacology, Schulich School of Medecine and Dentistry, Brain and Mind Institute, The University of Western Ontario, London, Ontario, Canada., Prado MAM; Robarts Research Institute, Department of Physiology and Pharmacology, Schulich School of Medecine and Dentistry, Brain and Mind Institute, The University of Western Ontario, London, Ontario, Canada.; Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario, Canada.; Department of Anatomy and Cell Biology, Brain and Mind Institute, The University of Western Ontario, London, Ontario, Canada., Chen L; State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China.; Institute of Molecular Medicine, Peking University, Beijing, China., Cheng H; State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China.; Institute of Molecular Medicine, Peking University, Beijing, China.; Research Unit of Mitochondria in Brain Diseases, Chinese Academy of Medical Sciences, PKU-Nanjing Institute of Translational Medicine, Nanjing, China., Li Y; State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China. yulongli@pku.edu.cn.; PKU-IDG/McGovern Institute for Brain Research, Beijing, China. yulongli@pku.edu.cn.; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China. yulongli@pku.edu.cn.
Jazyk: angličtina
Zdroj: Nature methods [Nat Methods] 2020 Nov; Vol. 17 (11), pp. 1139-1146. Date of Electronic Publication: 2020 Sep 28.
DOI: 10.1038/s41592-020-0953-2
Abstrakt: 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.
Databáze: MEDLINE