Elsevier

Brain Research

Volume 980, Issue 1, 1 August 2003, Pages 121-127
Brain Research

Research report
Sleep properties of CS mice with spontaneous rhythm splitting in constant darkness

https://doi.org/10.1016/S0006-8993(03)02947-0Get rights and content

Abstract

In mice, genetic differences between inbred strains have been shown for several parameters of sleep and circadian activity rhythms. Our previous studies have demonstrated that CS mice have three remarkable characteristics in the circadian rhythm of locomotor activity: (1) high activity both during the day and night, (2) unstable freerunning period and (3) spontaneous rhythm splitting. In order to characterize sleep properties of CS mice, we compared circadian sleep patterns of CS with those of C57BL/6J and C3H/He mice which have normal circadian activity rhythms. Although C57BL/6J and C3H/He mice exhibited clear daily sleep–wake rhythms in the amount of each sleep parameter (Awake, SWS, PS), CS mice did not show clear rhythms in these parameters. The differences were particularly conspicuous in PS; no apparent day–night differences in the amount of PS, PS counts and PS interval (the interval between successive PS episodes) in CS mice. In addition, the ratio of PS to total sleep time was significantly larger in CS mice than other strains. Of these parameters, the most considerable was PS latency which was extremely short and direct transition from Awake to PS without appearance of SWS frequently occurred in these mice. These results indicate that CS mice may be useful for the understanding of sleep mechanisms and its dysfunction.

Introduction

Although it is well known that several parameters of sleep are altered by genetic factors, the genes affecting sleep have not been identified in most cases. However, recent progress in molecular biology such as transgenic mice or knockout mice makes it possible to specify the gene involved in the mechanisms for the regulation of sleep. So far, several studies have been performed to examine alteration of sleep and sleep regulation in gene targeted mice. Of which, the most remarkable progress was made in orexin knockout mice which exhibit behavior similar to human narcolepsy [4].

In addition to this, evidence is increasing that the mechanisms underlying circadian and sleep regulation may be correlate with one another. For example, mice devoid of prion protein show alteration in both circadian activity rhythms and sleep [12], and the mutation of Clock which is involved in the core of the circadian clock mechanisms affects sleep homeostasis in mice [10]. A recent report also indicates that cryptochrome 1 and 2 genes (cry1 and 2), necessary for the generation of circadian rhythms, are implicated in sleep homeostatic regulation [18]. Therefore it is possible to speculate that mice with abnormal circadian rhythms also exhibit abnormal sleep properties.

CS strain of mice, which is an inbred line originally established from hybrids between the NBC and SII strain, has three remarkable characteristics in the circadian rhythm of locomotor activity; (1) high activity both during the day and night, (2) unstable freerunning activity with longer circadian period than 24 h and (3) spontaneous rhythm splitting under constant darkness (DD) [1]. CS is also sensitive to external stimuli and often shows a sudden cramp or a muscle attack. The circadian profiles of clock genes in the suprachiasmatic nucleus (SCN) during rhythm splitting are essentially the same as those observed under unsplit conditions [2], [3]. However, the mPer1 gene (one of the core clock genes) expression throughout the day is bimodal in the piriform and cingulate cortex, peaking in correspondence with two split components of locomotor activity. Thus it is interesting to examine sleep properties of CS mice. In this report, we attempted to characterize the sleep of CS mice comparing with other inbred strains (C3H/He and C57BL/6J) with normal circadian rhythmicity.

Section snippets

Animals and housing

Male CS (n=9), C57BL/6J (n=5) and C3H/He mice (n=4) were used. CS mice were maintained in our laboratory, and C57BL/6J and C3H/He were purchased from a dealer (Chubu-kagaku-shizai, Japan). All mice used in this experiment were between 8 and 12 weeks of age, and wheel-running activity (diameter of wheel, 10 cm) was recorded under light–dark (LD) 12:12-h cycles and DD. Chronobiology Kit (Stanford Software Systems) was used for the recording.

Surgery

All mice were deeply anesthetized with pentobarbital (50

Daily rhythmicity of Awake, SWS and PS in three strains

C57BL/6J and C3H/He mice exhibited a clear daily sleep–wake rhythm with large amounts of sleep during the light than during the dark under LD. The rhythmicity persisted under DD with essentially the similar pattern as that under LD (Fig. 2). The amount of Awake, SWS and PS was similar under LD and DD in these mice (Fig. 3).

The rhythmicity of CS mice under both LD and DD, however, were not so clear as other strains. In all sleep states, the daily rhythmicity became obscure (Fig. 2). These are

Discussion

Several studies have demonstrated genetic variations in sleep/wake architecture and EEG profiles in inbred mice [6], [7], [14], [16], [17]. For example, C57BL or C57BR mice are reported to show long PS sleep episodes, short SWS episodes and significant circadian variations under LD, while BALB/c mice have very short PS sleep episodes and unclear diurnal variations. Using CXB (derived from a cross between C57BL/6 and BALB/c) and BXD (derived from C57BL/6J and DBA/2) recombinant inbred lines,

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