Sensitive multicolor indicators for monitoring norepinephrine in vivo

Genetically encoded indicators engineered from G-protein-coupled receptors are important tools that enable high-resolution in vivo neuromodulator imaging. Here, we introduce a family of sensitive multicolor norepinephrine (NE) indicators, which includes nLightG (green) and nLightR (red). These tools report endogenous NE release in vitro, ex vivo and in vivo with improved sensitivity, ligand selectivity and kinetics, as well as a distinct pharmacological profile compared with previous state-of-the-art GRABNE indicators. Using in vivo multisite fiber photometry recordings of nLightG, we could simultaneously monitor optogenetically evoked NE release in the mouse locus coeruleus and hippocampus. Two-photon imaging of nLightG revealed locomotion and reward-related NE transients in the dorsal CA1 area of the hippocampus. Thus, the sensitive NE indicators introduced here represent an important addition to the current repertoire of indicators and provide the means for a thorough investigation of the NE system.


Zacharoula Kagiampaki
Valentin Rohner
Cedric Kiss
Sebastiano Curreli
Alexander Dieter
Maria Wilhelm
Masaya Harada
Sian N. Duss
Jan Dernic
Musadiq A. Bhat
Xuehan Zhou
Dr. Luca Ravotto
Tim Ziebarth
Laura Moreno Wasielewski
Latife Sönmez
Dietmar Benke
Prof. Dr. Bruno Weber
Johannes Bohacek
Andreas Reiner
J. Simon Wiegert
Tommaso Fellin
Tommaso Patriarchi

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