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Specific and behaviorally consequential astrocyte G q GPCR signaling attenuation in vivo with iβARK.
- Source :
-
Neuron [Neuron] 2021 Jul 21; Vol. 109 (14), pp. 2256-2274.e9. Date of Electronic Publication: 2021 Jun 16. - Publication Year :
- 2021
-
Abstract
- 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 <subscript>q</subscript> 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 <subscript>q</subscript> GPCR signaling. iβARK significantly attenuated G <subscript>q</subscript> GPCR Ca <superscript>2+</superscript> signaling in brain slices and, in vivo, altered behavioral responses, spared other GPCR responses, and did not alter astrocyte spontaneous Ca <superscript>2+</superscript> signals, morphology, electrophysiological properties, or gene expression in the striatum. Furthermore, brain-wide attenuation of astrocyte G <subscript>q</subscript> 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 <subscript>q</subscript> GPCR signaling within neural circuits in vivo.<br />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.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1097-4199
- Volume :
- 109
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Neuron
- Publication Type :
- Academic Journal
- Accession number :
- 34139149
- Full Text :
- https://doi.org/10.1016/j.neuron.2021.05.023