Locus coeruleus noradrenergic neurons have diverse activity patterns across species and biological context

The locus coeruleus (LC) brainstem cell group is evolutionarily conserved across vertebrates and influences both mind (cognition) and body (cardiorespiratory, metabolic, and immune functions) via two-putatively distinct-spontaneous activity patterns. Yet, the degree to which spontaneous LC firing rates and patterns are homogeneous across species has never been assessed due to inherently limited sample sizes. To remedy this, we pooled cross-species data from 20 laboratories to show that firing rates differ across species and are modulated by sex, age, and type of in vitro or in vivo preparation. Contrary to the prevailing dual-mode firing pattern schema, we observed patterns spread across a low-dimensional manifold, with subregions enriched for specific biological factors and neurodegenerative disease models. Our findings show considerable diversity in an ancestral vertebrate neuromodulatory system.

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Publication Details

Journal
Cell Reports
Published
2026-10-29
DOI
https://doi.org/10.1016/j.celrep.2026.118210
Primary Topic
Neurotransmitter Receptor Influence on Behavior
Type
article
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article

Locus coeruleus noradrenergic neurons have diverse activity patterns across species and biological context

Chayla R. Vazquez, Ehsan Arabzadeh, Michael A. Kelberman, Joshua P. Johansen et al.
Cell Reports
Neurotransmitter Receptor Influence on Behavior
article

Locus coeruleus noradrenergic neurons have diverse activity patterns across species and biological context

Chayla R. Vazquez, Ehsan Arabzadeh, Michael A. Kelberman, Joshua P. Johansen, Gina R. Poe, Roman Dvorkin, Alfred P. Kaye, Stephen D. Shea, Oscar Davy, Brandon Munn, James M. Shine, Elena M. Vazey, Erin Glennon, Chao‐Cheng Kuo, Ming‐Yuan Min, Zeinab Fazlali, Ellen M. Rodberg, Akira Uematsu, Mriganka Sur, Robert C. Froemke, Sonia Torres-Sánchez, Anna C. Sales, Alexandra C. Nowlan, Yadollah Ranjbar‐Slamloo, Ioannis S. Zouridis, Alicia Che, Anthony Edward Pickering, Charles Rodenkirch, Mohsen Omrani, Vincent Breton‐Provencher, John Tkaczynski, David M. Devilbiss, Joshua I. Gold, Jone Razquin, Gabrielle T Drummond, Nelson K. B. Totah, Meritxell Llorca-Torralba, Chloe J. Bair-Marshall, Jordan G. McCall, Barry D. Waterhouse, Anthony M. Downs, J. Yang, Zoé A. McElligott, Andrew McKinney, Qi Wang, Craig W. Berridge, Cristina Miguélez, David Weinshenker, Amelien Vreven, Liping Zhao, Jenny R. Kim, Rath Satyasambit, et al, Hsiu-Wen Yang, Xiaolong Jiang, Yang Liu, Hiroki Ito, Esther Berrocoso, Rong-Jian Liu
article en

Abstract

The locus coeruleus (LC) brainstem cell group is evolutionarily conserved across vertebrates and influences both mind (cognition) and body (cardiorespiratory, metabolic, and immune functions) via two-putatively distinct-spontaneous activity patterns. Yet, the degree to which spontaneous LC firing rates and patterns are homogeneous across species has never been assessed due to inherently limited sample sizes. To remedy this, we pooled cross-species data from 20 laboratories to show that firing rates differ across species and are modulated by sex, age, and type of in vitro or in vivo preparation. Contrary to the prevailing dual-mode firing pattern schema, we observed patterns spread across a low-dimensional manifold, with subregions enriched for specific biological factors and neurodegenerative disease models. Our findings show considerable diversity in an ancestral vertebrate neuromodulatory system.

Cell ReportsVol. 45(11)
University of North Carolina at Chapel Hill (US), Tokyo Institute of Technology (JP), Australian National University (AU), The University of Sydney (AU), University of Helsinki (FI), University of Wisconsin–Madison (US), National Sun Yat-sen University (TW), Emory University (US), University of California, Los Angeles (US), National Taiwan University (TW), University of the Basque Country (ES), National Institute of Informatics (JP), University of Colorado Boulder (US), Washington University in St. Louis (US), Queen's University (CA), University of Massachusetts Amherst (US), Cold Spring Harbor Laboratory (US), RIKEN Center for Brain Science (JP), Instituto de Salud Carlos III (ES), Yale University (US), University of Bristol (GB), Universidad de Cádiz (ES), NYU Langone Health (US), Centro de Investigación Biomédica en Red de Salud Mental (ES), National Center for PTSD (US), Max Planck Institute for Biological Cybernetics (DE), Biomedical Research and Innovation Institute of Cadiz (ES), Institute for Research in Fundamental Sciences (IR), Texas Children's Hospital (US), Virtua Health (US), Université Laval (CA), Weill Cornell Medicine (US), HiLIFE – Elämäntieteiden Instituutti (FI), Rhode Island College (US), New York University (US), Massachusetts Institute of Technology (US), National Institute of Advanced Industrial Science and Technology (JP), Columbia University (US), University of Pennsylvania (US), University of Tübingen (DE), Yokohama City University (JP), Chung Shan Medical University (TW)
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