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

• DOI: 10.1016/j.neuron.2019.02.037
• Publication Date: 2019-03-25T16:59:27Z
• Authors: Jiesi Feng; Changmei Zhang; Julieta E. Lischi...; Miao Jing; Jingheng Zhou; Huan Wang; Yajun Zhang; Ao Dong; Zhaofa Wu; Hao Wu; Weiyu Chen; Peng Zhang; Jing Zou; S. Andrew Hires; J. Julius Zhu; Guohong Cui; Dayu Lin; Jiulin Du; Yulong Li
• Keywords: Locus coeruleus

AbstractNorepinephrine (NE) and epinephrine (Epi), two key biogenic monoamine neurotransmitters, are involved in a wide range of physiological processes. However, their precise dynamics and regulation remain poorly characterized, in part due to limitations of available techniques for measuring these moleculesin vivo. Here, we developed a family ofGPCR Activation-BasedNE/Epi (GRABNE) sensors with a 230% peak ΔF/F0response to NE, good photostability, nanomolar-to-micromolar sensitivities, sub-second rapid kinetics, high specificity to NE vs. dopamine. Viral- or transgenic- mediated expression of GRABNEsensors were 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, GRABNEsensors are a robust tool for rapid and specific monitoring ofin vivoNE/Epi transmission in both physiological and pathological processes.