Specific and behaviorally consequential astrocyte G q GPCR signaling attenuation in vivo with iβARK.

Autor: Nagai J; Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; RIKEN Center for Brain Science, 2-1 Hirosawa Wako City, Saitama 351-0198, Japan., Bellafard A; Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA., Qu Z; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Yu X; Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 514 Burrill Hall, 407 S. Goodwin Ave, Urbana, IL 61801, USA., Ollivier M; Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA., Gangwani MR; Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA., Diaz-Castro B; Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA., Coppola G; Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA., Schumacher SM; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA., Golshani P; Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Integrative Center for Learning and Memory, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; West LA Veterans Affairs Medical Center, Los Angeles, CA 90073, USA; Intellectual and Developmental Disabilities Research Center, Los Angeles, CA, USA., Gradinaru V; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Khakh BS; Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Department of Neurobiology, University of California, David Geffen School of Medicine, Los Angeles, Los Angeles, CA 90095-1751, USA. Electronic address: bkhakh@mednet.ucla.edu.
Jazyk: angličtina
Zdroj: Neuron [Neuron] 2021 Jul 21; Vol. 109 (14), pp. 2256-2274.e9. Date of Electronic Publication: 2021 Jun 16.
DOI: 10.1016/j.neuron.2021.05.023
Abstrakt: Astrocytes respond to neurotransmitters and neuromodulators using G-protein-coupled receptors (GPCRs) to mediate physiological responses. Despite their importance, there has been no method to genetically, specifically, and effectively attenuate astrocyte G q GPCR pathways to explore consequences of this prevalent signaling mechanism in vivo. We report a 122-residue inhibitory peptide from β-adrenergic receptor kinase 1 (iβARK; and inactive D110A control) to attenuate astrocyte G q GPCR signaling. iβARK significantly attenuated G q GPCR Ca 2+ signaling in brain slices and, in vivo, altered behavioral responses, spared other GPCR responses, and did not alter astrocyte spontaneous Ca 2+ signals, morphology, electrophysiological properties, or gene expression in the striatum. Furthermore, brain-wide attenuation of astrocyte G q GPCR signaling with iβARK using PHP.eB adeno-associated viruses (AAVs), when combined with c-Fos mapping, suggested nuclei-specific contributions to behavioral adaptation and spatial memory. iβARK extends the toolkit needed to explore functions of astrocyte G q GPCR signaling within neural circuits in vivo.
Competing Interests: Declaration of interests The authors declare no competing interests relevant to this study. However, B.S.K. is a consultant for Third Rock Ventures.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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