Cortical region-specific sleep homeostasis in mice: effects of time of day and waking experience.
Guillaumin MCC., McKillop LE., Cui N., Fisher SP., Foster RG., de Vos M., Peirson SN., Achermann P., Vyazovskiy VV.
Sleep-wake history, wake behaviours, lighting conditions and circadian time influence sleep, but neither their relative contribution, nor the underlying mechanisms are fully understood. The dynamics of 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 non-rapid eye movement sleep (NREM), and the 24-h distribution of vigilance states. We hypothesised that the influence of extrinsic factors on sleep homeostasis, such as the time of day or wake behaviour, would manifest in systematic deviations between empirical SWA and model predictions. To test this hypothesis, we performed parameter estimation and tested model predictions using NREM 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 behaviours, 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 h.