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Distribution of waking in the individual hamsters during the short (top panel) and long photoperiod (lower panel) for 1-min intervals. The light-dark period is indicated by the vertical line and white and black bar at the top of the panels. Note the equal distribution of long waking bouts over the light and dark periods in the short photoperiod, contrasting the restriction of long waking bouts to the dark period in the long photoperiod.
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Running wheels are widely used in studies on biological rhythms. In mice wheel diameters have ranged from 11 cm to 23 cm. We provided mice with running wheels of two different sizes: 15 cm diameter and 11 cm diameter. The amount of running in the 12-h light:12-h dark condition and the endogenous period of wheel running in constant darkness was dete...
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... return to LP was paralleled by a remarkable increase in the light-dark difference of sleep and wak- ing (Table 1). The light-dark difference in the percent- age of time spent in waking increased from 6.1% ± 1.5% in SP to 20.5% ± 5.0% in LP (p < 0.05, two-tailed paired t-test), whereas total amount of sleep and waking within 24-h were unaffected (Table 1). The adaptation to LP considerably reduced the frequency and dura- tion of waking episodes and increased the frequency and duration of NREM sleep episodes in the light period (Table 2). In the dark period, NREM sleep epi- sode duration and the frequency and duration of REM sleep episodes was reduced. These changes are reflected in the distribution of waking of the individu- als (Fig. 1). After adaptation to LP, the longer waking episodes are restricted to the dark period, whereas in SP, they are equally distributed over the light and dark periods. In general, the waking episode duration did not differ between the photoperiods (Table 2). The mean 2-h values of the daily time course of the vigi- lance states in the two photoperiods is shown in Fig- ure 2. In SP, no vigilance state showed significant changes in the course of the 24-h day, whereas after adaptation to LP, they all did (ANOVA factor "2-h interval" SP: p > 0.2 for all vigilance states, LP: p < 0.00001 for all vigilance states). In all vigilance states, EEG power density over 24 h increased from SP to LP in the slow-wave range, whereas above 4 Hz, power density was not affected (Fig. 3). SWA in NREM sleep did not change in the course of 24 h in SP (Fig. 2 bottom panels, ANOVA fac- tor 2-h interval, p > 0.35), while in LP, it decreased sig- nificantly during the light, increased during the dark, and reached a maximum in the second half of the dark period (ANOVA factor 2-h interval p < 0.0001). SWA attained its lowest values in the second half of the light period and the first 2-h interval of the dark (Duncan multiple range test, p < ...
Citations
... Damm Reebs and St-Onge (2005) wykazano, że chomiki syryjskie mające możliwość wyboru, zdecydowanie preferowały większe kołowrotki (o średnicy 35 cm) w porównaniu z tymi o średnicy 23 cm. Podobne preferencje były również zaobserwowane w badaniach przeprowadzonych na myszach (Banjanin and Mrosovsky 2000;Deboer and Tobler, 2000). ...
Hamsters are very willingly kept in homes as companion animals. However, despite this, very hard to find reliable information on the requirements associated with the maintenance of these rodents. However, this does not change the fact that accommodation for a hamster must meet its normal physiological and behavioral needs, including resting, nesting, grooming, exploration, climbing, hiding, digging, searching, storing and chewing food. In order to check whether the level of public knowledge about keeping hamsters and their needs is adequate to the popularity of these rodents and whether it is sufficient to provide them with appropriate conditions in an average amateur breeding farm, a questionnaire survey was used in which as many as 80.3% of the respondents admitted to having or owning a hamster, and when asked about the appropriate size of the cage, they preferred larger sizes such as 80 x 40 cm (34.7%) or 90 x 45 cm (25.1%). However, noting that housing in small cages causes chronic stress in hamsters, the rule of thumb should be: the bigger the better. As many as 619 (80.1%) respondents state that a good amount of litter significantly improves hamster welfare. It has been proven that at least 40 cm of bedding really increases the level of hamster welfare. In addition, the absolute majority of respondents stated that the satisfaction of behavioral needs affects (22.6%) or is even dependent on hamster welfare (69.7%).The results obtained from the survey data highlight the need for new studies that would provide the opportunity to update the knowledge already available and correct unclear guidelines related to hamster housing. This would allow us to optimize the conditions of keeping hamsters in amateur breeding conditions and ensure their good or even high welfare.
... Mice allowed access to running wheels display a shorter free running circadian period (τ) than activityrestricted individuals [7][8][9]. The diameter of the running wheel used has been found to have an effect on total motor activity and phase delay in response to a light pulse [10]. ...
The activation of behaviour in a daily rhythm governed by the light cycle is a universal phenomenon among humans, laboratory mammals and other vertebrates. For mice, the active period is during the dark. We have quantified the increase in activity when the lights shut off (Light to Dark, L to D) using a generalized CNS arousal assay with 20 ms resolution, rather than traditional running wheels. Data analysis yielded the rare demonstration of an equation which precisely tracks this behavioural transition and, surprisingly, its reverse during D to L. This behavioural dynamic survives in constant darkness (experiment 2) and is hormone-sensitive (experiment 3). Finally (experiment 4), mice on a light schedule analogous to one which proved troublesome for U.S. Navy sailors, had dysregulated activity bursts which did not conform to the transitions between D and L. These experiments show the lawfulness of a behavioural phase transition and the consequence of deviating from that dynamic pattern. And, in a new way, they bring mathematics to the realm of behavioural neuroscience.
... Caffeine did not significantly change the amount of activity, but there was a trend towards increased activity during caffeine consumption. Increased activity can influence the period of the rest-activity rhythm, but is normally associated with shorter periods (Yamada et al., 1988(Yamada et al., , 1990Edgar et al., 1991;Mrosovsky, 1999;Deboer & Tobler, 2000). The data suggest that the chronic caffeine consumption via the drinking water increased the sensitivity of the endogenous circadian clock to light, and in accordance lengthened the period of the clock. ...
Caffeine is the most commonly used psychoactive stimulant worldwide. It reduces sleep and sleepiness by blocking access to the adenosine receptor. The level of adenosine increases during sleep deprivation, and is thought to induce sleepiness and initiate sleep. Light-induced phase shifts of the rest–activity circadian rhythms are mediated by light-responsive neurons of the suprachiasmatic nucleus (SCN) of the hypothalamus, where the circadian clock of mammals resides. Previous studies have shown that sleep deprivation reduces circadian clock phase-shifting capacity and decreases SCN neuronal activity. In addition, application of adenosine agonists and antagonists mimics and blocks, respectively, the effect of sleep deprivation on light-induced phase shifts in behaviour, suggesting a role for adenosine. In the present study, we examined the role of sleep deprivation in and the effect of caffeine on light responsiveness of the SCN. We performed in vivo electrical activity recordings of the SCN in freely moving mice, and showed that the sustained response to light of SCN neuronal activity was attenuated after 6 h of sleep deprivation prior to light exposure. Subsequent intraperitoneal application of caffeine was able to restore the response to light. Finally, we performed behavioural recordings in constant conditions, and found enhanced period lengthening during chronic treatment with caffeine in drinking water in constant light conditions. The data suggest that increased homeostatic sleep pressure changes circadian pacemaker functioning by reducing SCN neuronal responsiveness to light. The electrophysiological and behavioural data together provide evidence that caffeine enhances clock sensitivity to light.
... There were no behavioural differences between heterozygous and WT animals (data not shown), and therefore, the following results are from WT-KO comparisons only. First, we examined general cage activity of mice single-housed with the running wheel locked because several studies have shown that wheel running (a non-photic entraining stimulus) shortens the period of behavioural locomotor rhythms in DD (Edgar et al. 1991a,b;Kuroda et al. 1997;Deboer & Tobler, 2000;Harrington et al. 2007). Activity monitored with infrared motion sensors revealed no significant differences between genotypes in terms of average activity counts or circadian rhythmic amplitude in LD (Fig. 4A and B; Table 1). ...
Key points
Many time‐of‐day cues are mediated by G protein‐coupled signals within the clock centre (the suprachiasmatic nucleus, SCN) of the mammalian brain.
The role of G protein‐coupled inwardly rectifying potassium (GIRK) channels in SCN function and entrainment has yet to be determined.
GIRK channels are necessary for proper day‐time SCN neuronal resting membrane potential, neuropeptide Y signalling, and re‐entrainment to phase advances of the light–dark (LD) cycle.
GIRK channel activation is sufficient to mimic non‐photic phase shifts of the molecular clock.
GIRK channels act as an essential part of the non‐photic entrainment system, and could play a critical role in diseases such as epilepsy or addiction that have strong circadian comorbidities.
Abstract
G protein signalling within the central circadian oscillator, the suprachiasmatic nucleus (SCN), is essential for conveying time‐of‐day information. We sought to determine whether G protein‐coupled inwardly rectifying potassium channels (GIRKs) modulate SCN physiology and circadian behaviour. We show that GIRK current and GIRK2 protein expression are greater during the day. Pharmacological inhibition of GIRKs and genetic loss of GIRK2 depolarized the day‐time resting membrane potential of SCN neurons compared to controls. Behaviourally, GIRK2 knockout (KO) mice failed to shorten free running period in response to wheel access in constant darkness and entrained more rapidly to a 6 h advance of a 12 h:12 h light–dark (LD) cycle than wild‐type (WT) littermate controls. We next examined whether these effects were due to disrupted signalling of neuropeptide Y (NPY), which is known to mediate non‐photic phase shifts, attenuate photic phase shifts and activate GIRKs. Indeed, GIRK2 KO SCN slices had significantly fewer silent cells in response to NPY, likely contributing to the absence of NPY‐induced phase advances of PER2::LUC rhythms in organotypic SCN cultures from GIRK2 KO mice. Finally, GIRK channel activation is sufficient to cause a non‐photic‐like phase advance of PER2::LUC rhythms on a Per2 Luc +/− background. These results suggest that rhythmic regulation of GIRK2 protein and channel function in the SCN contributes to day‐time resting membrane potential, providing a mechanism for the fine tuning responses to non‐photic and photic stimuli. Further investigation could provide insight into disorders with circadian disruption comorbidities such as epilepsy and addiction, in which GIRK channels have been implicated.
... Because the behavioral shift was much larger than the shift in the SCN, it is highly unlikely that the behavioral shift was driven by a shift in the SCN. Previous studies have reported accelerated re-entrainment of behavior to a shifted LD cycle when the animals had access to a running wheel (Deboer and Tobler, 2000;Yamanaka et al., 2008). Nevertheless, the most intriguing aspect of this finding was the absence of a large shift in the SCN in the presence of a large behavioral shift. ...
The suprachiasmatic nucleus (SCN) adapts to both the external light-dark (LD) cycle and seasonal changes in day length. In short photoperiods, single-cell activity patterns are tightly synchronized (i.e., in phase); in long photoperiods, these patterns are relatively dispersed, causing lower amplitude rhythms. The limit cycle oscillator has been used to describe the SCN's circadian rhythmicity and predicts that following a given perturbation, high-amplitude SCN rhythms will shift less than low-amplitude rhythms. Some studies reported, however, that phase delays are larger when animals are entrained to a short photoperiod. Because phase advances and delays are mediated by partially distinct (i.e., nonoverlapping) biochemical pathways, we investigated the effect of a 4-h phase advance of the LD cycle in mice housed in either short (LD 8:16) or long (LD 16:8) photoperiods. In vitro recordings revealed a significantly larger phase advance in the SCN of mice entrained to short as compared to long photoperiods (4.2 ± 0.3 h v. 1.4 ± 0.9 h, respectively). Surprisingly, in mice with long photoperiods, the behavioral phase shift was larger than the phase shift of the SCN (3.7 ± 0.4 h v. 1.4 ± 0.9 h, respectively). To exclude a confounding influence of running-wheel activity on the magnitude of the shifts of the SCN, we repeated the experiments in the absence of running wheels and found similar shifts in the SCN in vitro in short and long days (3.0 ± 0.5 h v. 0.4 ± 0.9 h, respectively). Interestingly, removal of the running wheel reduced the phase-shifting capacity of mice in long days, leading to similar behavioral shifts in short and long photoperiods (1.0 ± 0.1 h v. 1.0 ± 0.4 h). As the behavioral shifts in the presence of wheels were larger than the shift of the SCN, it is suggested that additional, non-SCN neuronal networks in the brain are involved in regulating the timing of behavioral activity. On the basis of the phase shifts observed in vitro, we conclude that highly synchronized SCN networks with high-amplitude rhythms show a larger phase-shifting capacity than desynchronized networks of low amplitude.
... Rodents cannot carry an actigraph, and therefore, their rest-activity behavior is usually monitored by automated recording of running wheel activity rotations. As these recordings are influenced by several environmental cues [i.e., availability and size of the wheel, availability and quality of light (Banjanin and Mrosovsky 2000;Deboer and Tobler 2000a;Kas and Edgar 1999;Mrosovsky et al. 1998)], it is important to perform wheel-running experiments under well-defined environmental conditions. For instance, it has been shown that the availability of a running wheel influences the occurrence and distribution of sleep (Vyazovskiy et al. 2006). ...
The definition of what sleep
is depends on the method that is applied to record sleep. Behavioral and (electro)-physiological measures of sleep clearly overlap in mammals
and birds
, but it is often unclear how these two relate in other vertebrates and invertebrates. Homeostatic regulation of sleep, where the amount of sleep depends on the amount of previous waking, can be observed in physiology and behavior in all animals this was tested in. In mammals and birds, sleep is generally subdivided into two states, non-rapid eye movement (NREM) sleep
and REM sleep
. In mammals the combination of behavioral sleep and the changes in the slow-wave range of the NREM sleep electroencephalogram
(EEG) can explain and predict the occurrence and depth of sleep in great detail. For REM sleep this is far less clear. Finally, the discovery that slow-waves in the NREM sleep EEG are influenced locally on the cortex depending on prior waking behavior is an interesting new development that asks for an adaptation of the concept of homeostatic regulation
of sleep. Incorporating local sleep into models of sleep regulation is needed to obtain a comprehensive picture.
... After SCN lesions, the difference in TST ratio between the light and the dark period decreases, but sometimes a preference for sleep in the light period remains (Coindet et al., 1975). The latter may be a masking effect of light due to a suppression of activity (Deboer and Tobler, 2000) and direct induction of sleep by light (Alfoldi et al., 1991;Benca et al., 1998;Deboer et al., 2007b). In most SCN lesion experiments in mice and rats, performed under constant dark conditions, the amount of sleep over 24 h did not change, indicating that the endogenous clock does not determine the amount of sleep (Ibuka et al., 1980;Mistlberger et al., 1983;Tobler et al., 1983), but also here exceptions have been reported (Easton et al., 2004). ...
Sleep is regulated by circadian and homeostatic processes. The sleep homeostat keeps track of the duration of prior sleep and waking and determines the intensity of sleep. In mammals, the homeostatic process is reflected by the slow waves in the non-rapid eye movement (NREM) sleep electroencephalogram (EEG). The circadian process is controlled by a pacemaker located in the suprachiasmatic nucleus of the hypothalamus and provides the sleep homeostat with a circadian framework. This review summarizes the changes in sleep obtained after different chronobiological interventions (changes in photoperiod, light availability, and running wheel availability), the influence of mutations or lesions in clock genes on sleep, and research on the interaction between sleep homeostasis and the circadian clock. Research in humans shows that the period of consolidated waking during the day is a consequence of the interaction between an increasing homeostatic sleep drive and a circadian signal, which promotes waking during the day and sleep during the night. In the rat, it was shown that, under constant homeostatic sleep pressure, with similar levels of slow waves in the NREM sleep EEG at all time points of the circadian cycle, still a small circadian modulation of the duration of waking and NREM sleep episodes was observed. Under similar conditions, humans show a clear circadian modulation in REM sleep, whereas in the rat, a circadian modulation in REM sleep was not present. Therefore, in the rat, the sleep homeostatic modulation in phase with the circadian clock seems to amplify the relatively weak circadian changes in sleep induced by the circadian clock. Knowledge about the interaction between sleep and the circadian clock and the circadian modulation of sleep in other species than humans is important to better understand the underlying regulatory mechanisms.
... SCN firing rate is related to activity, with lower firing rate during bouts of spontaneous activity (Schaap and Meijer, 2001; van Oosterhout et al, 2012; Yamazaki et al, 1998). Increased activity has been shown to alter freerunning period (Deboer and Tobler, 2000; Edgar et al, 1991b; Mrosovsky, 1999; Yamada et al, 1988, 1990). Finally, scheduled confinement to a novel wheel typically leads to increased activity and can alter the phase angle of entrainment to a variety of lighting regimes (Sinclair and Mistlberger, 1997). ...
... As behavioral activity is able to influence the clock, one possibility is that SCN activity is changed as a consequence of the behavioral changes. We can reject this option for the following reasons: first, while increased activity has been shown to alter free-running period, higher activity is associated with shorter periods (Deboer and Tobler, 2000; Edgar et al, 1991b; Mrosovsky, 1999; Yamada ...
People with attention-deficit/hyperactivity disorder (ADHD) often experience sleep problems, and these are frequently exacerbated by the methylphenidate they take to manage their ADHD symptoms. Many of the changes to sleep are consistent with a change in the underlying circadian clock. The present study was designed to determine if methylphenidate alone could alter properties of the circadian clock. Young male mice were examined in light-dark cycles and in constant darkness and recordings were performed on behavioral activity, sleep, and electrical activity in the suprachiasmatic nucleus (SCN) of freely moving mice. Methylphenidate in the drinking water (0.08%) significantly increased activity in the mid-to-late night, and led to a delay in the onset of activity and sleep relative to the light-dark cycle. While locomotor levels returned to baseline after treatment ended, the phase angle of entrainment required at least a week to return to baseline levels. In constant darkness, the free-running period of both wheel-running and general locomotor rhythms was lengthened by methylphenidate. When the treatment ended, the free-running period either remained stable or only partially reverted to baseline levels. Methylphenidate also altered the electrical firing rate rhythms in the SCN. It induced a delay in the trough of the rhythm, an increment in rhythm amplitude, and a reduction in rhythm variability. These observations suggest that methylphenidate alters the underlying circadian clock. The observed changes are consistent with clock alterations that would promote sleep-onset insomnia.
... Arousal or increased voluntary behavioral activity, brought on by a variety of stimuli, exert changes in the circadian clock that are evidenced by period changes or phase shifts in the overt functions456789. For instance, wheel running activity is known to affect the period of the clock in a dose-dependent manner1011121314 and novelty-induced wheel running elicits phase shifts of the circadian activity rhythm [6,15]. Also in humans, behavioral activity during the day accelerates phase resetting to new time zones16171819 and physical exercise may have beneficial effects for circadian rhythm disorders related to dementia and aging [20]. ...
... Finally, stress has little effect on the circadian system of rats and hamsters [33,34], and corticosteroid receptors are absent in the SCN [35,36]. Instead, the excitatory SCN response may involve the participation of arousal or anxiety systems [10,37]. Neural structures that have been implicated in arousal responses include several nuclei in the diencephalon and brain stem, producing acetylcholine, histamine or norepinephrine and dopamine [38]. ...
Circadian rhythms are regulated by the suprachiasmatic nucleus (SCN), a small structure at the base of the hypothalamus. While light effects on the SCN are well established, little is known of behavioral effects. This study elucidates direct modulating action of behavioral activity on the SCN by use of in vivo electrophysiology recordings, assessments of general locomotor behavior, and video-tracking of mice. The results show suppression of SCN neuronal activity by spontaneous behavior, the magnitude being dependent on the intensity, duration and type of behavioral activity. The suppression was moderate (32% of circadian amplitude) for low-intensity behavior and considerable (59%) for locomotor activity. Mild manipulation of the animals had reversed effects on the SCN indicating that different mechanisms are involved in the regulatory effect of spontaneous versus induced activity. The results indicate that exercise at the proper time of the cycle can boost the amplitude of the rhythm of the SCN clock itself. This has potentially beneficial effects for other rhythmic functions that are under the control of the SCN.
... There is a difference in wheel diameter; Refinetti's running wheels have a diameter of 120mm whereas the data presented here was obtained from wheels of 180mm in diameter. The effect of running wheel size on mouse behavioural rhythms is known to have an effect on period lengths (Deboer and Tobler, 2000). Indeed, the present data demonstrate that mice with a running wheel of 150mm diameter display a shorter circadian period under DD conditions than animals with access to a running-wheel of 110mm in diameter. ...
... Further, the DD period Deober and Tobler (2000) describe for mice housed with access to a runningwheel of 150mm in diameter was 23.3 hours which is in close proximity to the period of 23.27 which we observed. However, direct comparisons with our data are slightly problematic as Deboer and Tobler (2000) did not use CD-1 mice in their study. Nonetheless, the findings demonstrated by Deober and Tobler (2000) offer a clear suggestion as to why the CD-1 period data described here is shorter than that described by Refinetti (2001;2004 and. ...
