| First Author | Nagai J | Year | 2021 |
| Journal | Neuron | Volume | 109 |
| Issue | 14 | Pages | 2256-2274.e9 |
| PubMed ID | 34139149 | Mgi Jnum | J:325336 |
| Mgi Id | MGI:6752421 | Doi | 10.1016/j.neuron.2021.05.023 |
| Citation | Nagai J, et al. (2021) Specific and behaviorally consequential astrocyte Gq GPCR signaling attenuation in vivo with ibetaARK. Neuron 109(14):2256-2274.e9 |
| abstractText | 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 Gq GPCR pathways to explore consequences of this prevalent signaling mechanism in vivo. We report a 122-residue inhibitory peptide from beta-adrenergic receptor kinase 1 (ibetaARK; and inactive D110A control) to attenuate astrocyte Gq GPCR signaling. ibetaARK significantly attenuated Gq 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 Gq GPCR signaling with ibetaARK using PHP.eB adeno-associated viruses (AAVs), when combined with c-Fos mapping, suggested nuclei-specific contributions to behavioral adaptation and spatial memory. ibetaARK extends the toolkit needed to explore functions of astrocyte Gq GPCR signaling within neural circuits in vivo. |
