Mice are the preferred mammalian species for genetic investigations of the role of proteins. The normal function of the prion protein (PrP) is unknown, although it plays a major role in the prion diseases, including fatal familial insomnia. We investigated its role in sleep and sleep regulation by comparing baseline recordings and the effects of sleep deprivation in PrP knockout mice (129/SV) and wild-type controls (129/SV × C57BL/6), which are the mice used for most gene targeting experiments and whose behavior is not well characterized. Although no difference was evident in the amount of vigilance states, the null mice exhibited a larger degree of sleep fragmentation than the wild-type with almost double the amount of short waking episodes. As in other rodents, cortical temperature closely reflected the time course of waking. The increase of slow-wave activity (SWA; mean EEG power density in the 0.25–4.0 Hz range) at waking to nonrapid eye movement (NREM) sleep transitions was faster and reached a lower level in the null mice than in the wild-type. The contribution of the lower frequencies (0.25–5.0 Hz) to the spectrum was smaller than in other rodents in all three vigilance states, and the distinction between NREM sleep and REM sleep was most marked in the theta band. After the sleep deprivation, SWA was increased, but the changes in EEG power density and SWA were more prominent and lasted longer in the PrP-null mice. Our results suggest that PrP plays a role in promoting sleep continuity.

Aging is associated with a deterioration of daily (circadian) rhythms in physiology and behavior. Deficits in the function of the central circadian pacemaker in the suprachiasmatic nucleus (SCN) have been implicated, but the responsible mechanisms have not been clearly delineated. In this report, we characterize the progression of rhythm deterioration in mice to 900 d of age. Longitudinal behavioral and sleep–wake recordings in up to 30-month-old mice showed strong fragmentation of rhythms, starting at the age of 700 d. Patch-clamp recordings in this age group revealed deficits in membrane properties and GABAergic postsynaptic current amplitude. A selective loss of circadian modulation of fast delayed-rectifier and A-type K⁺currents was observed. At the tissue level, phase synchrony of SCN neurons was grossly disturbed, with some subpopulations peaking in anti-phase and a reduction in amplitude of the overall multiunit activity rhythm. We propose that aberrant SCN rhythmicity in old animals—with electrophysiological arrhythmia at the single-cell level and phase desynchronization at the network level—can account for defective circadian function with aging.

Sleep is regulated by a homeostatic and a circadian process. Together these two processes determine most aspects of sleep and related variables like sleepiness and alertness. The two processes are known to be able to work independently, but also to both influence sleep and sleep related variables in an additive or more complex manner. The question remains whether the two processes are directly influencing each other. The present review summarizes evidence from behavioural and electroencephalographic determined sleep, electrophysiology, gene knock out mouse models, and mathematical modelling to explore whether sleep homeostasis can influence circadian clock functioning and vice versa. There is a multitude of data available showing parallel action or influence of sleep homeostatic mechanisms and the circadian clock on several objective and subjective variables related to sleep and alertness. However, the evidence of a direct influence of the circadian clock on sleep homeostatic mechanisms is sparse and more research is needed, particularly applying longer sleep deprivations that include a second night. The strongest evidence of an influence of sleep homeostatic mechanisms on clock functioning comes from sleep deprivation experiments, demonstrating an attenuation of phase shifts of the circadian rhythm to light pulses when sleep homeostatic pressure is increased. The data suggest that the circadian clock is less susceptible to light when sleep pressure is high. The available data indicate that a strong central clock will induce periods of deep sleep, which in turn will strengthen clock function. Both are therefore important for health and wellbeing. Weakening of one will also hamper functioning of the other. Shift work and jet lag are situations where one tries to adapt to zeitgebers in a condition where sleep is compromised. Adaptation to zeitgebers may be improved by introducing nap schedules to reduce sleep pressure, and through that increasing clock susceptibility to light.