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bioRxiv · 10.1101/2025.03.14.643122

Vagal afferent activation induces a NREM-sleep-like state with brain-body cooling, but locus coeruleus activation

Cherrad, N.·Foustoukos, G.·Fernandez, L. M.·Osorio-Forero, A.·Emmenegger, Y.·Franken, P.·Luthi, A.
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Abstract

Parasympathetic nervous system activity, vital for restorative sleep, is influenced by vagal sensory afferents, but how these shape brain-body correlates of sleep remains open. We investigated this by combining vagal sensory neuron (VSN) stimulation with EEG/EMG, heart rate, brain-body temperature, and noradrenergic locus coeruleus (LC) neuron population activity measures. Opto-/chemogenetic VSN manipulations in Vglut2-Cre mice were validated via in vitro synaptic physiology, cFos expression, and heart rate measures. Chemogenetic VSN stimulation during the resting phase induced a non-rapid-eye-movement sleep (NREMS)-like state with enriched, but homeostatically regulated, low-frequency (0.75-4 Hz) EEG activity, yet suppressed REMS. Simultaneously, brain-body temperatures dropped while LC activity increased. Recovery was gradual towards normal NREMS-REMS-cycles but accelerated by external warming, identifying cooling as key factor. We conclude that VSN activation can promote brain-body correlates as a continuum of normal NREM sleep while engaging forebrain neuromodulation, offering insights into mechanisms of sleep disruptions linked to autonomic dysregulation.

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Cherrad, N., Foustoukos, G., Fernandez, L. M., Osorio-Forero, A., Emmenegger, Y., Franken, P., Luthi, A.. 2025-03-15. Vagal afferent activation induces a NREM-sleep-like state with brain-body cooling, but locus coeruleus activation. https://doi.org/10.1101/2025.03.14.643122

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