A genetically encoded fluorescent sensor for monitoring spatiotemporal prostaglandin E2 dynamics in vivo

Prostaglandin E2 (PGE2) is an important lipid signaling molecule that regulates a wide range of physiological and pathological processes. However, its dynamics during these processes are largely unknown due to the lack of tools to directly visualize PGE2 with high spatiotemporal resolution. Here, we developed and characterized a genetically encoded G-protein-coupled receptor (GPCR) activation-based (GRAB) PGE2 sensor, which we call GRAB_PGE2-1.0 (PGE2-1.0), that has high specificity for PGE2, nanomolar affinity, rapid kinetics, and high spatial resolution when expressed both in vitro and in vivo. Using fiber-photometry recordings, we found that PGE2-1.0 can reliably monitor endogenous PGE2 dynamics in the preoptic area in the brain during acute inflammation. Wide-field in vivo imaging with PGE2-1.0 reveals spatial heterogeneity in cortex-wide PGE2 dynamics during acute inflammation and seizure. Thus, our PGE2-1.0 sensor can be used to detect endogenous PGE2 dynamics with high spatiotemporal resolution, providing a robust tool for studying PGE2 under specific physiological and pathological conditions.