Tonic and burst-like locus coeruleus stimulation distinctly shift network activity across the cortical hierarchy

Noradrenaline (NA) release from the locus coeruleus (LC) changes activity and connectivity in neuronal networks across the brain, modulating multiple behavioral states. NA release is mediated by both tonic and burst-like LC activity. However, it is unknown whether the functional changes in target areas depend on these firing patterns. Using optogenetics, photometry, electrophysiology and functional magnetic resonance imaging in mice, we show that tonic and burst-like LC firing patterns elicit brain responses that hinge on their distinct NA release dynamics. During moderate tonic LC activation, NA release engages regions associated with associative processing, while burst-like stimulation biases the brain toward sensory processing. These activation patterns locally couple with increased astrocytic and inhibitory activity and change the brain's topological configuration in line with the hierarchical organization of the cerebral cortex. Together, these findings reveal how the LC-NA system achieves a nuanced regulation of global circuit operations.

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Publication Details

Journal
Nature Neuroscience
Published
2024-09-16
DOI
https://doi.org/10.1038/s41593-024-01755-8
Citations
72
Primary Topic
Neural dynamics and brain function
Type
article
Field-Weighted Citation Impact
24.33

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article

Tonic and burst-like locus coeruleus stimulation distinctly shift network activity across the cortical hierarchy

Brandon Munn, James M. Shine, Christina Grimm, Sian N. Duss et al.
72 citations
Nature Neuroscience
Neural dynamics and brain function
24.33
article

Tonic and burst-like locus coeruleus stimulation distinctly shift network activity across the cortical hierarchy

Brandon Munn, James M. Shine, Christina Grimm, Sian N. Duss, Maria Wilhelm, Johannes Bohacek, Nikolaos Karalis, Nicole Wenderoth, Valerio Zerbi, Tommaso Patriarchi, Daniel Razansky, Mattia Privitera, Stefan Frässle
article en
72 citations

Abstract

Noradrenaline (NA) release from the locus coeruleus (LC) changes activity and connectivity in neuronal networks across the brain, modulating multiple behavioral states. NA release is mediated by both tonic and burst-like LC activity. However, it is unknown whether the functional changes in target areas depend on these firing patterns. Using optogenetics, photometry, electrophysiology and functional magnetic resonance imaging in mice, we show that tonic and burst-like LC firing patterns elicit brain responses that hinge on their distinct NA release dynamics. During moderate tonic LC activation, NA release engages regions associated with associative processing, while burst-like stimulation biases the brain toward sensory processing. These activation patterns locally couple with increased astrocytic and inhibitory activity and change the brain's topological configuration in line with the hierarchical organization of the cerebral cortex. Together, these findings reveal how the LC-NA system achieves a nuanced regulation of global circuit operations.

Nature NeuroscienceVol. 27(11)
University of Geneva (CH), Centre National de la Recherche Scientifique (FR), The University of Sydney (AU), Inserm (FR), University of Zurich (CH), Helmholtz Zentrum München (DE), ETH Zurich (CH), Sorbonne Université (FR), Institute for Biomedical Engineering (CH), Assistance Publique – Hôpitaux de Paris (FR), Centre d'Imagerie BioMedicale (CH), Institut du Cerveau (FR), École Polytechnique Fédérale de Lausanne (CH), Technical University of Munich (DE), Friedrich Miescher Institute (CH)
National Science Foundation, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Eidgenössische Technische Hochschule Zürich, Medical Research Council, National Health and Medical Research Council
Openalex Percentile: Top 0%
Neural dynamics and brain function
24.33
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