Infraslow noradrenergic locus coeruleus activity fluctuations are gatekeepers of the NREM-REM sleep cycle

Alejandro Osorio-Forero; Georgios Foustoukos; Romain Cardis; Najma Cherrad; Christiane Devenoges; Laura M J Fernandez; Anita Lüthi

doi:10.1038/s41593-024-01822-0

Infraslow noradrenergic locus coeruleus activity fluctuations are gatekeepers of the NREM-REM sleep cycle

Alejandro Osorio-Forero, Georgios Foustoukos, Romain Cardis, Najma Cherrad, Christiane Devenoges, Laura M J Fernandez, Anita Lüthi

Netherlands Institute for Neuroscience (NIN)

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

5 Citations (Scopus)

Abstract

The noradrenergic locus coeruleus (LC) regulates arousal levels during wakefulness, but its role in sleep remains unclear. Here, we show in mice that fluctuating LC neuronal activity partitions non-rapid-eye-movement sleep (NREMS) into two brain-autonomic states that govern the NREMS-REMS cycle over ~50-s periods; high LC activity induces a subcortical-autonomic arousal state that facilitates cortical microarousals, whereas low LC activity is required for NREMS-to-REMS transitions. This functional alternation regulates the duration of the NREMS-REMS cycle by setting permissive windows for REMS entries during undisturbed sleep while limiting these entries to maximally one per ~50-s period during REMS restriction. A stimulus-enriched, stress-promoting wakefulness was associated with longer and shorter levels of high and low LC activity, respectively, during subsequent NREMS, resulting in more microarousal-induced NREMS fragmentation and delayed REMS onset. We conclude that LC activity fluctuations are gatekeepers of the NREMS-REMS cycle and that this role is influenced by adverse wake experiences.

Original language	English
Pages (from-to)	84-96
Journal	Nature Neuroscience
Volume	28
DOIs	https://doi.org/10.1038/s41593-024-01822-0
Publication status	Published - Jan 2025

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10.1038/s41593-024-01822-0

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@article{3379d6fff4f14919971de5bd081a6f72,

title = "Infraslow noradrenergic locus coeruleus activity fluctuations are gatekeepers of the NREM-REM sleep cycle",

abstract = "The noradrenergic locus coeruleus (LC) regulates arousal levels during wakefulness, but its role in sleep remains unclear. Here, we show in mice that fluctuating LC neuronal activity partitions non-rapid-eye-movement sleep (NREMS) into two brain-autonomic states that govern the NREMS-REMS cycle over ~50-s periods; high LC activity induces a subcortical-autonomic arousal state that facilitates cortical microarousals, whereas low LC activity is required for NREMS-to-REMS transitions. This functional alternation regulates the duration of the NREMS-REMS cycle by setting permissive windows for REMS entries during undisturbed sleep while limiting these entries to maximally one per ~50-s period during REMS restriction. A stimulus-enriched, stress-promoting wakefulness was associated with longer and shorter levels of high and low LC activity, respectively, during subsequent NREMS, resulting in more microarousal-induced NREMS fragmentation and delayed REMS onset. We conclude that LC activity fluctuations are gatekeepers of the NREMS-REMS cycle and that this role is influenced by adverse wake experiences.",

author = "Alejandro Osorio-Forero and Georgios Foustoukos and Romain Cardis and Najma Cherrad and Christiane Devenoges and Fernandez, {Laura M J} and Anita L{\"u}thi",

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T1 - Infraslow noradrenergic locus coeruleus activity fluctuations are gatekeepers of the NREM-REM sleep cycle

AU - Osorio-Forero, Alejandro

AU - Foustoukos, Georgios

AU - Cardis, Romain

AU - Cherrad, Najma

AU - Devenoges, Christiane

AU - Fernandez, Laura M J

AU - Lüthi, Anita

PY - 2025/1

Y1 - 2025/1

N2 - The noradrenergic locus coeruleus (LC) regulates arousal levels during wakefulness, but its role in sleep remains unclear. Here, we show in mice that fluctuating LC neuronal activity partitions non-rapid-eye-movement sleep (NREMS) into two brain-autonomic states that govern the NREMS-REMS cycle over ~50-s periods; high LC activity induces a subcortical-autonomic arousal state that facilitates cortical microarousals, whereas low LC activity is required for NREMS-to-REMS transitions. This functional alternation regulates the duration of the NREMS-REMS cycle by setting permissive windows for REMS entries during undisturbed sleep while limiting these entries to maximally one per ~50-s period during REMS restriction. A stimulus-enriched, stress-promoting wakefulness was associated with longer and shorter levels of high and low LC activity, respectively, during subsequent NREMS, resulting in more microarousal-induced NREMS fragmentation and delayed REMS onset. We conclude that LC activity fluctuations are gatekeepers of the NREMS-REMS cycle and that this role is influenced by adverse wake experiences.

AB - The noradrenergic locus coeruleus (LC) regulates arousal levels during wakefulness, but its role in sleep remains unclear. Here, we show in mice that fluctuating LC neuronal activity partitions non-rapid-eye-movement sleep (NREMS) into two brain-autonomic states that govern the NREMS-REMS cycle over ~50-s periods; high LC activity induces a subcortical-autonomic arousal state that facilitates cortical microarousals, whereas low LC activity is required for NREMS-to-REMS transitions. This functional alternation regulates the duration of the NREMS-REMS cycle by setting permissive windows for REMS entries during undisturbed sleep while limiting these entries to maximally one per ~50-s period during REMS restriction. A stimulus-enriched, stress-promoting wakefulness was associated with longer and shorter levels of high and low LC activity, respectively, during subsequent NREMS, resulting in more microarousal-induced NREMS fragmentation and delayed REMS onset. We conclude that LC activity fluctuations are gatekeepers of the NREMS-REMS cycle and that this role is influenced by adverse wake experiences.

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JO - Nature Neuroscience

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