Cortical region–specific sleep homeostasis in mice: effects of time of day and waking experience

Abstract

Sleep–wake history, wake behaviors, lighting conditions, and circadian time influence sleep, but neither their relative contribution nor the underlying mechanisms are fully understood. The dynamics of electroencephalogram (EEG) slow-wave activity (SWA) during sleep can be described using the two-process model, whereby the parameters of homeostatic Process S are estimated using empirical EEG SWA (0.5–4 Hz) in nonrapid eye movement sleep (NREMS), and the 24 hr distribution of vigilance states. We hypothesized that the influence of extrinsic factors on sleep homeostasis, such as the time of day or wake behavior, would manifest in systematic deviations between empirical SWA and model predictions. To test this hypothesis, we performed parameter estimation and tested model predictions using NREMS SWA derived from continuous EEG recordings from the frontal and occipital cortex in mice. The animals showed prolonged wake periods, followed by consolidated sleep, both during the dark and light phases, and wakefulness primarily consisted of voluntary wheel running, learning a new motor skill or novel object exploration. Simulated SWA matched empirical levels well across conditions, and neither waking experience nor time of day had a significant influence on the fit between data and simulation. However, we consistently observed that Process S declined during sleep significantly faster in the frontal than in the occipital area of the neocortex. The striking resilience of the model to specific wake behaviors, lighting conditions, and time of day suggests that intrinsic factors underpinning the dynamics of Process S are robust to extrinsic influences, despite their major role in shaping the overall amount and distribution of vigilance states across 24 hr.

Dynamic changes in cerebral and peripheral markers of glutamatergic signaling across the human sleep-wake cycle

“…Here, we quantified at the same circadian time in 20 study participants the effects of prolonged wakefulness and recovery sleep on the extracellular concentrations of Glu, GLX and GABA in two predefined voxels located in the cortex (dlPFC) and the BG. Both these regions show pronounced waking-induced changes in mGluR5 availability (Holst et al, 2017) and are thought to contribute importantly to sleep homeostasis (Dahan et al, 2006;Léna et al, 2005;Guillaumin et al, 2018). Consistent with our previous study (Holst et al, 2017), sleep deprivation caused no reliable changes in these metabolites in the cortex (Fig.…”

Sleep deprivation triggers somatostatin neurons in prefrontal cortex to initiate nesting and sleep via the preoptic and lateral hypothalamus

“…Excitability throughout the neocortex increases with time spent awake 71 . In awake and behaving animals, local delta NREM-like oscillations develop in different regions of the neocortex following use-dependent activity [72][73][74][75][76] . It is well established that neocortical NOS1-expressing cells become active throughout the neocortex during sleep deprivation 41,42 .…”

The role of the hypothalamus in cortical arousal and sleep homeostasis

“…Since optical stimulation may affect the animal's sleep and behavior due to local heating (Owen et al, 2019) or due to direct effects of light (Tyssowski and Gray, 2019), we also analyzed a cohort of GFP animals as a control group, which received the AAV-DIO-EGFP injection and were implanted with an optical fiber in the same area. EEG and EMG electrodes were also surgically implanted, as has been done previously (Guillaumin et al, 2018), to enable the identification of the sleep-wake state of the animal.…”