Genetic determinants of sleep regulation in inbred mice.

Genetic variation in the expression and regulation of sleep was assessed in six inbred mice strains (AK, C, B6, BR, D2, 129). The amount, distribution, and fragmentation of the behavioral states wakefulness (W), slow-wave sleep (SWS), and paradoxical sleep (PS), as well as EEG delta power in SWS, were determined and compared among strains and between baseline and recovery from a 6-hour sleep deprivation (SD) starting at lights-on. In baseline, the most striking strain differences concerned sleep amount, the onset and duration of the main rest period, and SWS fragmentation. The time course of delta power in SWS during the main rest period was similar between strains. Immediately following the SD, high delta power values were reached (higher for AK than for 129). However, the relative increase in delta power, compared to the first 6 hours of the baseline rest period, was not strain-specific. Over the first 6 hours of recovery, W was decreased and PS increased in AK, B6, BR, and 129. In C and D2, time spent in any of the states was not affected by the SD. In contrast, in the recovery dark period, SWS and PS were invariably increased. In recovery, SWS fragmentation was strongly reduced for D2, resulting in the disappearance of the strain differences observed in baseline. Since these inbred strains are fully homozygous and thus can be considered genetic clones, the sleep-related strain differences reported here can be attributed to differences in genotype. Therefore, this study provides a basis for the identification of genetic factors underlying sleep and its regulation.