Characterization of the bout durations of sleep and wakefulness

STUDY OBJECTIVES (a) Develop a new statistical approach to describe the microarchitecture of wakefulness and sleep in mice; (b) evaluate differences among inbred strains in this microarchitecture; (c) compare results when data are scored in 4-s versus 10-s epochs. DESIGN Studies in male mice of four inbred strains: AJ, C57BL/6, DBA and PWD. EEG/EMG were recorded for 24h and scored independently in 4-s and 10-s epochs. MEASUREMENTS AND RESULTS Distribution of bout durations of wakefulness, NREM and REM sleep in mice has two distinct components, i.e., short and longer bouts. This is described as a spike (short bouts) and slab (longer bouts) distribution, a particular type of mixture model. The distribution in any state depends on the state the mouse is transitioning from and can be characterized by three parameters: the number of such bouts conditional on the previous state, the size of the spike, and the average length of the slab. While conventional statistics such as time spent in state, average bout duration, and number of bouts show some differences between inbred strains, this new statistical approach reveals more major differences. The major difference between strains is their ability to sustain long bouts of NREM sleep or wakefulness. Scoring mouse sleep/wake in 4-s epochs offered little new information when using conventional metrics but did when evaluating the microarchitecture based on this new approach. CONCLUSIONS Standard statistical approaches do not adequately characterize the microarchitecture of mouse behavioral state. Approaches based on a spike-and-slab provide a quantitative description.

[1]  A. Malafosse,et al.  Genetic determinants of sleep regulation in inbred mice. , 1999, Sleep.

[2]  C. Saper,et al.  Hypothalamic regulation of sleep and circadian rhythms , 2005, Nature.

[3]  S. Simasko,et al.  Novel analysis of sleep patterns in rats separates periods of vigilance cycling from long-duration wake events , 2009, Behavioural Brain Research.

[4]  Jon T. Willie,et al.  Narcolepsy in orexin Knockout Mice Molecular Genetics of Sleep Regulation , 1999, Cell.

[5]  Nancy J Kopell,et al.  Mathematical model of network dynamics governing mouse sleep-wake behavior. , 2007, Journal of neurophysiology.

[6]  M. Blumberg,et al.  Dynamics of sleep-wake cyclicity in developing rats. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[7]  T Mochizuki,et al.  Delayed orexin signaling consolidates wakefulness and sleep: physiology and modeling. , 2008, Journal of neurophysiology.

[8]  L. Amaral,et al.  Dynamics of sleep-wake transitions during sleep , 2001, cond-mat/0112280.

[9]  M. Blumberg,et al.  Developmental divergence of sleep‐wake patterns in orexin knockout and wild‐type mice , 2007, The European journal of neuroscience.

[10]  Seiji Nishino,et al.  Specificity of direct transition from wake to REM sleep in orexin/ataxin-3 transgenic narcoleptic mice , 2009, Experimental Neurology.

[11]  H. Stanley,et al.  Common scale-invariant patterns of sleep-wake transitions across mammalian species. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[12]  D Chollet,et al.  The Homeostatic Regulation of Sleep Need Is under Genetic Control , 2001, The Journal of Neuroscience.

[13]  R. Joho,et al.  Kv3 potassium channels control the duration of different arousal states by distinct stochastic and clock‐like mechanisms , 2006, The European journal of neuroscience.

[14]  Dimitris N. Metaxas,et al.  Novel method for high-throughput phenotyping of sleep in mice. , 2007, Physiological genomics.

[15]  S. McKnight,et al.  NPAS2 as a transcriptional regulator of non-rapid eye movement sleep: genotype and sex interactions. , 2006, Proceedings of the National Academy of Sciences of the United States of America.