SLEEP AND SLEEP REGULATION IN NORMAL AND PRION PROTEIN-DEFICIENT MICE

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, incl uding fatal familial insomnia. We investigated its role in sleep and s leep regulation by comparing baseline recordings and the effects of sl eep deprivation in PrP knockout mice (129/SV) and wild-type controls ( 129/SV x C57BL/6), which are the mice used for most gene targeting exp eriments and whose behavior is not well characterized. Although no dif ference was evident in the amount of vigilance states, the null mice e xhibited a larger degree of sleep fragmentation than the wild-type wit h almost double the amount of short waking episodes. As in other roden ts, 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) steep tr ansitions was faster and reached a lower level in the null mice than i n the wild-type. The contribution of the lower frequencies (0.25-5.0 H z) to the spectrum was smaller than in other rodents in all three vigi lance states, and the distinction between NREM sleep and REM sleep was most marked in the theta band. After the sleep deprivation, SWA was i ncreased, but the changes in EEG power density and SWA were more promi nent and lasted longer in the PrP-null mice. Our results suggest that PrP plays a role in promoting sleep continuity.