Topographic structure and function of locus coeruleus norepinephrine neurons

Norepinephrine (NE) is released throughout most of the central nervous system by neurons in the locus coeruleus (LC). We found a relationship between the morphologies, gene expression, and activity of LC-NE neurons in mice. Axonal projections of individual neurons were extensive but largely confined to subsets of brain regions. Axonal projections and graded gene expression correlated with locations of cell bodies in LC. In a behavioral task requiring ongoing learning from actions, neurons in dorsal LC projecting to the cerebral cortex were excited when mice made a different choice from the previous one and by reward prediction errors, a signal driving learning. Background activity of neurons in ventral LC was higher when mice ignored stimuli indicating potential reward availability. These observations reveal a topographically organized structure and function of a neurotransmitter system and show that it contains learning signals for flexible behavior.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-04-10
DOI
https://doi.org/10.64898/2026.04.10.717727
Primary Topic
Neural dynamics and brain function
Type
article
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article

Topographic structure and function of locus coeruleus norepinephrine neurons

Nicholas A. Lusk, Matthew I. Becker, Jeremiah Y. Cohen, Tamara Casper et al.
bioRxiv (Cold Spring Harbor Laboratory)
Neural dynamics and brain function
article

Topographic structure and function of locus coeruleus norepinephrine neurons

Nicholas A. Lusk, Matthew I. Becker, Jeremiah Y. Cohen, Tamara Casper, Joshua H. Siegle, S Chen, Alex T. Piet, Alessio Paolo Buccino, Polina Kosillo, Tim Jarsky, María Camila Vergara, Kanghoon Jung, Zhixiao Su, Mathew T. Summers, Thomas Chartrand, Naveen Ouellette, Douglas R. Ollerenshaw, Jayaram Chandrashekar, Xiaoyin Chen, Nick Dee, Yoh Isogai, Kimberly A. Smith, Han Hou, Carolyn M. Eng, Samantha L. Black, Cameron Arshadi, Adam K. Glaser, Drew Friedmann, Kenta M. Hagihara, Windy Ho, Sharmishtaa Seshamani, Elliot J Phillips, Mara C.P. Rue, Karel Svoboda, Camilo Laiton, John R. Rohde, Brian R Lee, Rajvi Javeri, Ella Hilton-VanOsdall, Matthew Jungert, Megan Koch, Krista Blake, Audrey McCutcheon, Atlas Jordan, Sonya Vasquez, Holly Myers, Di Wang, Kaelin Wulf, Peter Grotz, Olivia Ho-Shing, Kamiliam Nasirova, Anish Bhaswanth Chakka, Margaret Lee
article en

Abstract

Norepinephrine (NE) is released throughout most of the central nervous system by neurons in the locus coeruleus (LC). We found a relationship between the morphologies, gene expression, and activity of LC-NE neurons in mice. Axonal projections of individual neurons were extensive but largely confined to subsets of brain regions. Axonal projections and graded gene expression correlated with locations of cell bodies in LC. In a behavioral task requiring ongoing learning from actions, neurons in dorsal LC projecting to the cerebral cortex were excited when mice made a different choice from the previous one and by reward prediction errors, a signal driving learning. Background activity of neurons in ventral LC was higher when mice ignored stimuli indicating potential reward availability. These observations reveal a topographically organized structure and function of a neurotransmitter system and show that it contains learning signals for flexible behavior.

bioRxiv (Cold Spring Harbor Laboratory)
Allen Institute for Brain Science (US), Allen Institute (US)
Openalex Percentile: Top 26%
Neural dynamics and brain function
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