A four-state Markov model of sleep-wakefulness dynamics along light/dark cycle in mice

Behavioral states alternate between wakefulness ( wk ), rapid eye movement ( rem ) and non- rem ( nrem ) sleep at time scale of hours i.e ., light and dark cycle rhythms and from several tens of minutes to seconds ( i.e ., brief awakenings during sleep). Using statistical analysis of bout duration, Markov chains of sleep- wk dynamics and quantitative EEG analysis, we evaluated the influence of light/dark ( ld ) changes on brain function along the sleep- wk cycle. Bout duration ( bd ) histograms and Kaplan-Meier ( km ) survival curves of wk showed a bimodal statistical distribution, suggesting that two types of wk do exist: brief- wk ( wkb ) and long- wk ( wkl ). Light changes modulated specifically wkl bouts, increasing its duration during active/dark period. In contrast, wkb , nrem and rem bd histograms and km curves did not change significantly along ld cycle. Hippocampal eeg of both types of wk were different: in comparison wkb showed a lower spectral power in fast gamma and fast theta bands and less emg tone. After fitting a four-states Markov chain to mice hypnograms, moreover in states transition probabilities matrix was found that: in dark/active period, state-maintenance probability of wkl increased, and probability of wkl to nrem transition decreased; the opposite was found in light period, favoring the hypothesis of the participation of brief wk into nrem - rem intrinsic sleep cycle, and the role of wkl in SWS homeostasis. In conclusion, we propose an extended Markov model of sleep using four stages ( wkl , nrem , rem , wkb ) as a fully adequate model accounting for both modulation of sleep-wake dynamics based on the differential regulation of long- wk (high gamma/theta) epochs during dark and light phases.