Search bioRxiv⌕ Search

Biology subjects

Cherrad, N.

Publications and source records attributed to Cherrad, N..

2 recordsLinked to original sources

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

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.

neuroscience↗

Locus coeruleus activity fluctuations set a non-reducible timeframe for mammalian NREM-REM sleep cycles

The noradrenergic locus coeruleus (LC) is vital for brain states underlying wakefulness, whereas its roles for sleep remain uncertain. Combining mouse sleep-wake monitoring, behavioral manipulations, LC fiber photometry and closed-loop optogenetics, we found that LC neuronal activity partitioned non-rapid-eye-movement sleep (NREMS) into alternating brain and autonomic states that rule the NREMS-REMS cycle. High LC activity levels generated an autonomic-subcortical arousal state that facilitated cortical microarousals, while low levels were obligatory for REMS entries. Timed optogenetic LC inhibition revealed that this functional alternation set the duration of the NREMS-REMS cycle by ruling REMS entries during undisturbed sleep and when pressure for REMS was high. A stimulus-enriched, stress-promoting wakefulness increased high LC activity levels at the expense of low ones in subsequent NREMS, fragmenting NREMS through microarousals and delaying REMS onset. We conclude that LC activity fluctuations gatekeep the NREM-REMS cycle over recurrent infraslow intervals, but they also convey vulnerability to adverse wake experiences.

neuroscience↗