A photoswitchable GPCR-based opsin for presynaptic inhibition.

Autor: Copits BA; Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: bcopits@wustl.edu., Gowrishankar R; Center of Excellence in the Neurobiology of Addiction, Pain, and Emotion, Departments of Anesthesiology and Pain Medicine, and Pharmacology, University of Washington, Seattle, WA, USA., O'Neill PR; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA; Shirley and Stefan Hatos Center for Neuropharmacology, Semel Institute, Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA., Li JN; Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA., Girven KS; Center of Excellence in the Neurobiology of Addiction, Pain, and Emotion, Departments of Anesthesiology and Pain Medicine, and Pharmacology, University of Washington, Seattle, WA, USA., Yoo JJ; Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA., Meshik X; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA., Parker KE; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA., Spangler SM; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA., Elerding AJ; Center of Excellence in the Neurobiology of Addiction, Pain, and Emotion, Departments of Anesthesiology and Pain Medicine, and Pharmacology, University of Washington, Seattle, WA, USA., Brown BJ; Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA., Shirley SE; Center of Excellence in the Neurobiology of Addiction, Pain, and Emotion, Departments of Anesthesiology and Pain Medicine, and Pharmacology, University of Washington, Seattle, WA, USA., Ma KKL; Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA., Vasquez AM; Department of Pharmacology, University of California San Diego, San Diego, CA, USA., Stander MC; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA., Kalyanaraman V; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA., Vogt SK; Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA., Samineni VK; Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA., Patriarchi T; Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland., Tian L; Department of Biochemistry and Molecular Medicine, University of California Davis, Davis, CA, USA., Gautam N; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA., Sunahara RK; Department of Pharmacology, University of California San Diego, San Diego, CA, USA., Gereau RW 4th; Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA; Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, USA., Bruchas MR; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA; Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, USA; Center of Excellence in the Neurobiology of Addiction, Pain, and Emotion, Departments of Anesthesiology and Pain Medicine, and Pharmacology, University of Washington, Seattle, WA, USA. Electronic address: mbruchas@uw.edu.
Jazyk: angličtina
Zdroj: Neuron [Neuron] 2021 Jun 02; Vol. 109 (11), pp. 1791-1809.e11. Date of Electronic Publication: 2021 May 11.
DOI: 10.1016/j.neuron.2021.04.026
Abstrakt: Optical manipulations of genetically defined cell types have generated significant insights into the dynamics of neural circuits. While optogenetic activation has been relatively straightforward, rapid and reversible synaptic inhibition has proven more elusive. Here, we leveraged the natural ability of inhibitory presynaptic GPCRs to suppress synaptic transmission and characterize parapinopsin (PPO) as a GPCR-based opsin for terminal inhibition. PPO is a photoswitchable opsin that couples to G i/o signaling cascades and is rapidly activated by pulsed blue light, switched off with amber light, and effective for repeated, prolonged, and reversible inhibition. PPO rapidly and reversibly inhibits glutamate, GABA, and dopamine release at presynaptic terminals. Furthermore, PPO alters reward behaviors in a time-locked and reversible manner in vivo. These results demonstrate that PPO fills a significant gap in the neuroscience toolkit for rapid and reversible synaptic inhibition and has broad utility for spatiotemporal control of inhibitory GPCR signaling cascades.
Competing Interests: Declaration of interests R.W.G and M.R.B. are cofounders of Neurolux Inc., a neuroscience technology company, but no related technology was used in this study. All other authors declare no competing interests.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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