Heterogeneous pericoerulear neurons tune arousal and exploratory behaviours

Andrew T. Luskin, Li Li, Xiaonan Fu, Madison M. Martin, Kelsey Barcomb, Kasey S. Girven, Taylor Blackburn, Bailey A. Wells, Sarah T. Thai, Esther M. Li, Akshay N. Rana, Rhiana C. Simon, Li Sun, Lei Gao, Alexandria D. Murry, Sam A. Golden, Garret D. Stuber, Christopher P. Ford, Liangcai Gu and Michael R. Bruchas ()
Additional contact information
Andrew T. Luskin: University of Washington
Li Li: University of Washington
Xiaonan Fu: University of Washington
Madison M. Martin: University of Washington
Kelsey Barcomb: Anschutz Medical Campus
Kasey S. Girven: University of Washington
Taylor Blackburn: University of Washington
Bailey A. Wells: University of Washington
Sarah T. Thai: University of Washington
Esther M. Li: University of Washington
Akshay N. Rana: University of Washington
Rhiana C. Simon: University of Washington
Li Sun: University of Washington
Lei Gao: University of Washington
Alexandria D. Murry: University of Washington
Sam A. Golden: University of Washington
Garret D. Stuber: University of Washington
Christopher P. Ford: Anschutz Medical Campus
Liangcai Gu: University of Washington
Michael R. Bruchas: University of Washington

Nature, 2025, vol. 643, issue 8071, 437-447

Abstract: Abstract As the primary source of noradrenaline in the brain, the locus coeruleus (LC) regulates arousal, avoidance and stress responses1,2. However, how local neuromodulatory inputs control LC function remains unresolved. Here we identify a population of transcriptionally, spatially and functionally diverse GABAergic (γ-aminobutyric acid-producing) neurons in the LC dendritic field that receive distant inputs and modulate modes of LC firing to control global arousal levels and arousal-related processing and behaviours. We define peri-LC anatomy using viral tracing and combine single-cell RNA sequencing with spatial transcriptomics to molecularly define both LC noradrenaline-producing and peri-LC cell types. We identify several neuronal cell types that underlie peri-LC functional diversity using a series of complementary neural circuit approaches in behaving mice. Our findings indicate that LC and peri-LC neurons are transcriptionally, functionally and anatomically heterogenous neuronal populations that modulate arousal and avoidance states. Defining the molecular, cellular and functional diversity of the LC and peri-LC provides a roadmap for understanding the neurobiological basis of arousal, motivation and neuropsychiatric disorders.

Date: 2025
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DOI: 10.1038/s41586-025-08952-w

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