A Genetically Encoded Fluorescent Sensor for Rapid and Specific In Vivo Detection of Norepinephrine

Summary Norepinephrine (NE) is a key biogenic monoamine neurotransmitter involved in a wide range of physiological processes. However, its precise dynamics and regulation remain poorly characterized, in part due to limitations of available techniques for measuring NE in vivo . Here, we developed a family of GPCR activation-based NE (GRAB NE ) sensors with a 230% peak ΔF/F 0 response to NE, good photostability, nanomolar-to-micromolar sensitivities, sub-second kinetics, and high specificity. Viral- or transgenic-mediated expression of GRAB NE sensors was able to detect electrical-stimulation-evoked NE release in the locus coeruleus (LC) of mouse brain slices, looming-evoked NE release in the midbrain of live zebrafish, as well as optogenetically and behaviorally triggered NE release in the LC and hypothalamus of freely moving mice. Thus, GRAB NE sensors are robust tools for rapid and specific monitoring of in vivo NE transmission in both physiological and pathological processes. Video Abstract Download video (31MB) Help with mp4 files