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Next-generation multicolor indicators for in vivo imaging of norepinephrine

Norepinephrine (NE) is a critical neuromodulator that dynamically shapes brain states and behavior. Genetically encoded fluorescent NE indicators have enabled in vivo visualization of NE release, yet their limited sensitivity and spectral flexibility constrain widespread use in complex experimental...

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Main Authors: Rohner, Valentin Lu (Author) , Curreli, Sebastiano (Author) , Lamothe-Molina, Paul J. (Author) , Kagiampaki, Zacharoula (Author) , Yee, Andrew G. (Author) , Nardin, Chiara (Author) , Eschholz, Lena (Author) , Dieter, Alexander (Author) , Foustoukos, Georgios (Author) , Milanese, Paola (Author) , Banterle, Lila (Author) , Childs, Thomas (Author) , Canziani, Annika (Author) , Dernic, Jan (Author) , Ravotto, Luca (Author) , Bhat, Musadiq A. (Author) , Sönmez, Latife (Author) , Wasielewski, Laura Moreno (Author) , Ziebarth, Tim (Author) , Molnar, Marton Istvan (Author) , Huang, Gaoyang (Author) , Masseck, Olivia Andrea (Author) , Weber, Bruno (Author) , Reiner, Andreas (Author) , Lüthi, Anita (Author) , Ford, Christopher P. (Author) , Wiegert, Simon (Author) , Ruediger, Sarah (Author) , Fellin, Tommaso (Author) , Patriarchi, Tommaso (Author)
Format: Article (Journal)
Language:English
Published: March 2026
In: Nature methods
Year: 2026, Volume: 23, Issue: 3, Pages: 636-652
ISSN:1548-7105
DOI:10.1038/s41592-026-03006-z
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41592-026-03006-z
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41592-026-03006-z
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Author Notes:Valentin Lu Rohner, Sebastiano Curreli, Paul J. Lamothe-Molina, Zacharoula Kagiampaki, Andrew G. Yee, Chiara Nardin, Lena Eschholz, Alexander Dieter, Georgios Foustoukos, Paola Milanese, Lila Banterle, Thomas Childs, Annika Canziani, Jan Dernic, Luca Ravotto, Musadiq A. Bhat, Latife Sönmez, Laura Moreno Wasielewski, Tim Ziebarth, Marton Istvan Molnar, Gaoyang Huang, Olivia Andrea Masseck, Bruno Weber, Andreas Reiner, Anita Lüthi, Christopher P. Ford, J. Simon Wiegert, Sarah Ruediger, Tommaso Fellin & Tommaso Patriarchi
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Summary:Norepinephrine (NE) is a critical neuromodulator that dynamically shapes brain states and behavior. Genetically encoded fluorescent NE indicators have enabled in vivo visualization of NE release, yet their limited sensitivity and spectral flexibility constrain widespread use in complex experimental paradigms. Here we developed next-generation green and red fluorescent NE indicators, named nLightG2 and nLightR2, respectively. We systematically compared them to other state-of-the-art indicators and found that both indicators improve the detection of endogenous NE release across preparations. Using dual-color photometry, both nLightG2 and nLightR2 could reliably track physiologically relevant NE release along with neuronal activity in different brain areas. Using two-photon imaging, nLightR2 permitted simultaneous dual-color imaging of NE release and astrocytic activity in the hippocampus, while nLightG2 enabled the detection of spatiotemporally discrete NE release events in the visual cortex of awake mice. This improved toolkit will prove useful for dissecting the spatiotemporal complexity of norepinephrine signaling in the brain.
Item Description:Online veröffentlicht: 26. Februar 2026
Gesehen am 16.03.2026
Physical Description:Online Resource
ISSN:1548-7105
DOI:10.1038/s41592-026-03006-z

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