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22 novembre 2021
- doi: 10.1016/j.cub.2021.09.041
- issn: 0960-9822
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A. Osorio-Forero et al., « Noradrenergic circuit control of non-REM sleep substates. », Serveur académique Lausannois, ID : 10.1016/j.cub.2021.09.041
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To understand what makes sleep vulnerable in disease, it is useful to look at how wake-promoting mechanisms affect healthy sleep. Wake-promoting neuronal activity is inhibited during non-rapid-eye-movement sleep (NREMS). However, sensory vigilance persists in NREMS in animals and humans, suggesting that wake promotion could remain functional. Here, we demonstrate that consolidated mouse NREMS is a brain state with recurrent fluctuations of the wake-promoting neurotransmitter noradrenaline on the ∼50-s timescale in the thalamus. These fluctuations occurred around mean noradrenaline levels greater than the ones of quiet wakefulness, while noradrenaline (NA) levels declined steeply in REMS. They coincided with a clustering of sleep spindle rhythms in the forebrain and with heart-rate variations, both of which are correlates of sensory arousability. We addressed the origins of these fluctuations by using closed-loop optogenetic locus coeruleus (LC) activation or inhibition timed to moments of low and high spindle activity during NREMS. We could suppress, lock, or entrain sleep-spindle clustering and heart-rate variations, suggesting that both fore- and hindbrain-projecting LC neurons show coordinated infraslow activity variations in natural NREMS. Noradrenergic modulation of thalamic, but not cortical, circuits was required for sleep-spindle clustering and involved NA release into primary sensory and reticular thalamic nuclei that activated both α1- and β-adrenergic receptors to cause slowly decaying membrane depolarizations. Noradrenergic signaling by LC constitutes a vigilance-promoting mechanism that renders mammalian NREMS vulnerable to disruption on the close-to-minute timescale through sustaining thalamocortical and autonomic sensory arousability. VIDEO ABSTRACT.