A bistable inhibitory optoGPCR for multiplexed optogenetic control of neural circuits.

Autor: Wietek J; Department of Brain Sciences, Weizmann Institute of Science, Rehovot, Israel. jonas.wietek@gmail.com.; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel. jonas.wietek@gmail.com.; Neuroscience Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany. jonas.wietek@gmail.com., Nozownik A; Center for Molecular Neurobiology, Hamburg, Germany.; Paris Brain Institute, Institut du Cerveau (ICM), CNRS UMR 7225, INSERM U1127, Sorbonne Université, Paris, France., Pulin M; Center for Molecular Neurobiology, Hamburg, Germany.; Laboratory of Sensory Processing, Brain Mind Institute, Faculty of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland., Saraf-Sinik I; Department of Brain Sciences, Weizmann Institute of Science, Rehovot, Israel.; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel., Matosevich N; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel., Gowrishankar R; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA.; Center for Excellence in the Neurobiology of Addiction, Pain and Emotion, University of Washington, Seattle, WA, USA., Gat A; Department of Brain Sciences, Weizmann Institute of Science, Rehovot, Israel.; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel., Malan D; Institut für Physiologie I, University of Bonn, Bonn, Germany., Brown BJ; Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA., Dine J; Department of Brain Sciences, Weizmann Institute of Science, Rehovot, Israel.; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel.; Boehringer Ingelheim Pharma GmbH & Co. KG; CNS Diseases, Biberach an der Riss, Germany., Imambocus BN; LIMES-Institute, University of Bonn, Bonn, Germany., Levy R; Department of Brain Sciences, Weizmann Institute of Science, Rehovot, Israel.; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel., Sauter K; Center for Molecular Neurobiology, Hamburg, Germany., Litvin A; Department of Brain Sciences, Weizmann Institute of Science, Rehovot, Israel.; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel., Regev N; Department of Physiology and Pharmacology, Tel Aviv University, Tel Aviv, Israel., Subramaniam S; Department of Brain Sciences, Weizmann Institute of Science, Rehovot, Israel.; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel., Abrera K; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA., Summarli D; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA., Goren EM; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.; University of Michigan, Ann Arbor, MI, USA., Mizrachi G; Department of Brain Sciences, Weizmann Institute of Science, Rehovot, Israel.; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel., Bitton E; Department of Brain Sciences, Weizmann Institute of Science, Rehovot, Israel.; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel., Benjamin A; Department of Brain Sciences, Weizmann Institute of Science, Rehovot, Israel.; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel., Copits BA; Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA., Sasse P; Institut für Physiologie I, University of Bonn, Bonn, Germany., Rost BR; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.; Neuroscience Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany., Schmitz D; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.; Neuroscience Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.; Bernstein Center for Computational Neuroscience, Berlin, Germany.; Einstein Center for Neurosciences, Berlin, Germany.; Max Delbrück Center for Molecular Medicine, Berlin, Germany., Bruchas MR; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA.; Center for Excellence in the Neurobiology of Addiction, Pain and Emotion, University of Washington, Seattle, WA, USA.; Department of Pharmacology, University of Washington, Seattle, WA, USA., Soba P; LIMES-Institute, University of Bonn, Bonn, Germany.; Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Oren-Suissa M; Department of Brain Sciences, Weizmann Institute of Science, Rehovot, Israel.; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel., Nir Y; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.; Department of Physiology and Pharmacology, Tel Aviv University, Tel Aviv, Israel.; Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel., Wiegert JS; Center for Molecular Neurobiology, Hamburg, Germany.; MCTN, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany., Yizhar O; Department of Brain Sciences, Weizmann Institute of Science, Rehovot, Israel. ofer.yizhar@weizmann.ac.il.; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel. ofer.yizhar@weizmann.ac.il.
Jazyk: angličtina
Zdroj: Nature methods [Nat Methods] 2024 Jul; Vol. 21 (7), pp. 1275-1287. Date of Electronic Publication: 2024 May 29.
DOI: 10.1038/s41592-024-02285-8
Abstrakt: Information is transmitted between brain regions through the release of neurotransmitters from long-range projecting axons. Understanding how the activity of such long-range connections contributes to behavior requires efficient methods for reversibly manipulating their function. Chemogenetic and optogenetic tools, acting through endogenous G-protein-coupled receptor pathways, can be used to modulate synaptic transmission, but existing tools are limited in sensitivity, spatiotemporal precision or spectral multiplexing capabilities. Here we systematically evaluated multiple bistable opsins for optogenetic applications and found that the Platynereis dumerilii ciliary opsin (PdCO) is an efficient, versatile, light-activated bistable G-protein-coupled receptor that can suppress synaptic transmission in mammalian neurons with high temporal precision in vivo. PdCO has useful biophysical properties that enable spectral multiplexing with other optogenetic actuators and reporters. We demonstrate that PdCO can be used to conduct reversible loss-of-function experiments in long-range projections of behaving animals, thereby enabling detailed synapse-specific functional circuit mapping.
(© 2024. The Author(s).)
Databáze: MEDLINE