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Grimm, C.* ; Duss, S.N.* ; Privitera, M.* ; Munn, B.R.* ; Karalis, N.* ; Frässle, S.* ; Wilhelm, M.* ; Patriarchi, T.* ; Razansky, D. ; Wenderoth, N.* ; Shine, J.M.* ; Bohacek, J.* ; Zerbi, V.*

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

Nat. Neurosci., DOI: 10.1038/s41593-024-01755-8 (2024)

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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 type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Noradrenergic System; Neuronal-activity; Hemodynamic-response; Ceruleus Neurons; Activation; Modulation; Monkey; State; Performance; Attention

ISSN (print) / ISBN 1097-6256

e-ISSN 1546-1726

Journal Nature Neuroscience

Publisher Nature Publishing Group

Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Biological and Medical Imaging (IBMI)

Grants SNSF AMBIZIONE
Swiss National Science Foundation (SNSF)
ETH Zurich
SNSF
Swiss 3R Competence Center
Basel Research Centre for Child Health
Hochschulmedizin Zurich Flagship Project STRESS
National Health and Medical Research Council
ETH