A chemogenetic approach for dopamine imaging with tunable sensitivity.

Autor: Labouesse MA; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland.; Neuroscience Center Zurich, University and ETH Zürich, Zürich, Switzerland.; Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland., Wilhelm M; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland.; Institute for Neuroscience, ETH Zurich, Zurich, Switzerland., Kagiampaki Z; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland., Yee AG; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, USA., Denis R; Department of Pharmacology & Physiology, Faculty of Medicine, SNC and CIRCA Research groups, Université de Montréal, Montréal, QC, Canada.; Department of Neurosciences, Faculty of Medicine, SNC and CIRCA Research groups, Université de Montréal, Montréal, QC, Canada., Harada M; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland., Gresch A; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland., Marinescu AM; Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland., Otomo K; Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland., Curreli S; Optical Approaches to Brain Function Laboratory, Istituto Italiano di Tecnologia, Genova, Italy., Serratosa Capdevila L; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland., Zhou X; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland., Cola RB; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland., Ravotto L; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland., Glück C; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland., Cherepanov S; Institute of Cellular and Integrative Neuroscience, University of Strasbourg, Strasbourg, France., Weber B; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland.; Neuroscience Center Zurich, University and ETH Zürich, Zürich, Switzerland., Zhou X; Eli Lilly and Company, Indianapolis, IN, USA., Katner J; Eli Lilly and Company, Indianapolis, IN, USA., Svensson KA; Eli Lilly and Company, Indianapolis, IN, USA., Fellin T; Optical Approaches to Brain Function Laboratory, Istituto Italiano di Tecnologia, Genova, Italy., Trudeau LE; Department of Pharmacology & Physiology, Faculty of Medicine, SNC and CIRCA Research groups, Université de Montréal, Montréal, QC, Canada.; Department of Neurosciences, Faculty of Medicine, SNC and CIRCA Research groups, Université de Montréal, Montréal, QC, Canada., Ford CP; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, USA., Sych Y; Institute of Cellular and Integrative Neuroscience, University of Strasbourg, Strasbourg, France., Patriarchi T; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland. patriarchi@pharma.uzh.ch.; Neuroscience Center Zurich, University and ETH Zürich, Zürich, Switzerland. patriarchi@pharma.uzh.ch.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 02; Vol. 15 (1), pp. 5551. Date of Electronic Publication: 2024 Jul 02.
DOI: 10.1038/s41467-024-49442-3
Abstrakt: Genetically-encoded dopamine (DA) sensors enable high-resolution imaging of DA release, but their ability to detect a wide range of extracellular DA levels, especially tonic versus phasic DA release, is limited by their intrinsic affinity. Here we show that a human-selective dopamine receptor positive allosteric modulator (PAM) can be used to boost sensor affinity on-demand. The PAM enhances DA detection sensitivity across experimental preparations (in vitro, ex vivo and in vivo) via one-photon or two-photon imaging. In vivo photometry-based detection of optogenetically-evoked DA release revealed that DETQ administration produces a stable 31 minutes window of potentiation without effects on animal behavior. The use of the PAM revealed region-specific and metabolic state-dependent differences in tonic DA levels and enhanced single-trial detection of behavior-evoked phasic DA release in cortex and striatum. Our chemogenetic strategy can potently and flexibly tune DA imaging sensitivity and reveal multi-modal (tonic/phasic) DA signaling across preparations and imaging approaches.
(© 2024. The Author(s).)
Databáze: MEDLINE
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