Optogenetic approaches for dissecting neuromodulation and GPCR signaling in neural circuits

•Optogenetic tools provide precise spatial and temporal control of GPCR signaling.•Light-sensitive proteins can be engineered for GPCR-specific applications.•Advances in imaging technology are paving new pathways in vitro and in vivo GPCR research.

Optogenetics has revolutionized neuroscience by providing means to control cell signaling with spatiotemporal control in discrete cell types. In this review, we summarize four major classes of optical tools to manipulate neuromodulatory GPCR signaling: opsins (including engineered chimeric receptors); photoactivatable proteins; photopharmacology through caging - photoswitchable molecules; fluorescent protein based reporters and biosensors. Additionally, we highlight technologies to utilize these tools in vitro and in vivo, including Cre dependent viral vector expression and two-photon microscopy. These emerging techniques targeting specific members of the GPCR signaling pathway offer an expansive base for investigating GPCR signaling in behavior and disease states, in addition to paving a path to potential therapeutic developments.