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Technology Development Initiative – Paper of the Month – October 2023

Sensitive multicolor indicators for monitoring norepinephrine in vivo

Published in Nature Methods (2023)

A figure from this article. Image copyright: Nature.

A figure from this article. Image copyright: Nature.

Authors

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

Paper presented by Dr. Reinis Svarcbahs and selected by the NIDA TDI Paper of the Month Committee

Publication Brief Description

Norepinephrine (NE) is involved in mediating psychostimulant-associated behaviors such as drug discrimination, reinstatement of drug seeking and sensitization. Existing GPCR-based NE sensors are based on alpha-2a adrenergic receptors and do not exhibit the kinetic properties needed to investigate in vivo NE dynamics in response to different drugs. Kagiampaki et al. developed a new set of fluorescent indicators based on the alpha-1a adrenergic receptors (nLightG and nLightR, G for green and R for red respectively). These novel NE sensors have improved selectivity for NE over DA and have approximately ten times faster kinetics compared to the previous generation NE indicators. The nLight sensors combined with fiber photometry and two-photon imaging could be used to investigate spatial and temporal aspects of NE signaling in animal models of substance use disorder.


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

Sensitive multicolor indicators for monitoring norepinephrine in vivo Journal Article

In: Nat Methods, vol. 20, no. 9, pp. 1426–1436, 2023, ISSN: 1548-7105.

Abstract | Links

@article{pmid37474807,
title = {Sensitive multicolor indicators for monitoring norepinephrine in vivo},
author = {Zacharoula Kagiampaki and Valentin Rohner and Cedric Kiss and Sebastiano Curreli and Alexander Dieter and Maria Wilhelm and Masaya Harada and Sian N Duss and Jan Dernic and Musadiq A Bhat and Xuehan Zhou and Luca Ravotto and Tim Ziebarth and Laura Moreno Wasielewski and Latife Sönmez and Dietmar Benke and Bruno Weber and Johannes Bohacek and Andreas Reiner and J Simon Wiegert and Tommaso Fellin and Tommaso Patriarchi},
url = {https://pubmed.ncbi.nlm.nih.gov/37474807/},
doi = {10.1038/s41592-023-01959-z},
issn = {1548-7105},
year = {2023},
date = {2023-09-01},
urldate = {2023-09-01},
journal = {Nat Methods},
volume = {20},
number = {9},
pages = {1426--1436},
abstract = {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 GRAB 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.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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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 GRAB 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.

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  • https://pubmed.ncbi.nlm.nih.gov/37474807/
  • doi:10.1038/s41592-023-01959-z

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