Vertebrate Cone Opsins Enable Sustained and Highly Sensitive Rapid Control of Gi/o Signaling in Anxiety Circuitry

• Published in: Neuron (Cambridge, Mass.) Mass.), 2014-03, Vol.81 (6), p.1263-1273
• Main Authors: Masseck, Olivia A., Spoida, Katharina, Dalkara, Deniz, Maejima, Takashi, Rubelowski, Johanna M., Wallhorn, Lutz, Deneris, Evan S., Herlitze, Stefan
• Format: Article
• Language: English
• Subjects: Animals; Anxiety - metabolism; Anxiety - physiopathology; Behavior, Animal - physiology; Cone Opsins - metabolism; GTP-Binding Protein alpha Subunits, Gi-Go - metabolism; Humans; Light; Mice; Neurons - metabolism; Receptor, Serotonin, 5-HT1A - metabolism; Retinal Cone Photoreceptor Cells - metabolism; Rod Opsins - metabolism; Signal Transduction - physiology
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2014.01.041

G protein-coupled receptors (GPCRs) coupling to Gi/o signaling pathways are involved in the control of important physiological functions, which are difficult to investigate because of the limitation of tools to control the signaling pathway with precise kinetics and specificity. We established two vertebrate cone opsins, short- and long-wavelength opsin, for long-lasting and repetitive activation of Gi/o signaling pathways in vitro and in vivo. We demonstrate for both opsins the repetitive fast, membrane-delimited, ultra light-sensitive, and wavelength-dependent activation of the Gi/o pathway in HEK cells. We also show repetitive control of Gi/o pathway activation in 5-HT1A receptor domains in the dorsal raphe nucleus (DRN) in brain slices and in vivo, which is sufficient to modulate anxiety behavior in mice. Thus, vertebrate cone opsins represent a class of tools for understanding the role of Gi/o-coupled GPCRs in health and disease. [Display omitted] •Cone opsins can repetitively activate the Gi/o pathway in vitro and in vivo.•Cone opsins are very light-sensitive in comparison to ChR and eNpHR variants.•Cone opsins allow dual Gi/o pathway activation using different wavelengths of light.•Cone opsins are suitable to control anxiety circuits. Masseck et al. develop vertebrate cone opsins to repetitively activate Gi/o pathways in vitro and in mammalian anxiety circuits with wavelength specificity. The vOpsins represent a class of optogenetic tools for understanding the role of GPCRs in health and disease.