The hypothalamic link between arousal and sleep homeostasis in mice

Abstract

Sleep and wakefulness are not simple, homogenous all-or-none states but represent a spectrum of substates, distinguished by behavior, levels of arousal, and brain activity at the local and global levels. Until now, the role of the hypothalamic circuitry in sleep–wake control was studied primarily with respect to its contribution to rapid state transitions. In contrast, whether the hypothalamus modulates within-state dynamics (state “quality”) and the functional significance thereof remains unexplored. Here, we show that photoactivation of inhibitory neurons in the lateral preoptic area (LPO) of the hypothalamus of adult male and female laboratory mice does not merely trigger awakening from sleep, but the resulting awake state is also characterized by an activated electroencephalogram (EEG) pattern, suggesting increased levels of arousal. This was associated with a faster build-up of sleep pressure, as reflected in higher EEG slow-wave activity (SWA) during subsequent sleep. In contrast, photoinhibition of inhibitory LPO neurons did not result in changes in vigilance states but was associated with persistently increased EEG SWA during spontaneous sleep. These findings suggest a role of the LPO in regulating arousal levels, which we propose as a key variable shaping the daily architecture of sleep–wake states.

Neuroprotective effect of Ziziphi Spinosae Semen on rats with p-chlorophenylalanine-induced insomnia via activation of GABAA receptor

“…The pathogenesis of insomnia is extremely complex. It has been shown that insomnia is closely related to the hypothalamus and the hippocampus, and extensive hypothalamic damage leads to complete insomnia ( Yamagata et al, 2021 ; Bajaj and Kaur, 2022 ). Previous studies have also shown that when hippocampal cells are damaged and the volume of the hippocampus shrinks to a certain extent, the rapid eye movement (REM) sleep time can be reduced ( Forouzanfar et al, 2021 ; Tapp et al, 2022 ).…”

Noradrenergic Tone is Not Required for Neuronal Activity-Induced Rebound Sleep in Zebrafish

“…One idea is that homeostatic sleep need reflects the overall level of brain activity integrated over prior waking. While sleep pressure has traditionally been associated with wake duration (Borbély and Achermann, 1999), not all waking behaviour involves equivalent neuronal activity (Fisher et al, 2016; Milinski et al, 2021) and within-waking arousal states can modulate the accumulation of sleep pressure (Yamagata et al, 2021; Vassalli and Franken, 2017). Experiments in zebrafish have demonstrated that acutely and transiently elevating neuronal activity with arousing drugs such as caffeine is followed by increased sleep (Reichert et al, 2019).…”

A non-lemniscal thalamic interface connecting alerting sensory cues to internal states in mice

“…This is not only because arousal is relatively easy to be observed externally, but also because it powerfully modulates perception, cognition, and behavior 1 . Through decades of studies, it is clear now that arousal level is strongly regulated by intrinsic factors such as circadian rhythms 5 , energy homeostasis 6 and sleep homeostasis 7 . Besides, changes in arousal level are also commonly observed when one is exposed to behaviorally meaningful environmental cues, especially the alerting ones 8 , 9 .…”