Effects of aging on the circadian rhythm of wheel-running activity in C57BL/6 mice

1997 ◽  
Vol 273 (6) ◽  
pp. R1957-R1964 ◽  
Author(s):  
Verónica S. Valentinuzzi ◽  
Kathryn Scarbrough ◽  
Joseph S. Takahashi ◽  
Fred W. Turek
Keyword(s):  
Wheel Running ◽  
Activity Rhythm ◽  
Laboratory Mouse ◽  
Active Phase ◽  
Constant Darkness ◽  
Age Difference ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Activity Onset ◽  
Old Mice

The effects of age on the circadian clock system have been extensively studied, mainly in two rodent species, the laboratory rat and the golden hamster. However, less information is available on how aging alters circadian rhythmicity in a commonly studied rodent animal model, the mouse. Therefore, in the present study we compared the rhythm of wheel-running activity in adult (6–9 mo) and old (19–22 mo) C57BL/6J mice maintained under different lighting conditions for a period of 4 mo. During this period, mice were subjected to phase advances and phase delays of the light-dark (LD) cycle and eventually to constant darkness (DD). In LD (12 h light, 12 h dark), old mice exhibited delayed activity onset relative to light offset and an increase in the variability of activity onset compared with adult mice. After a 4-h phase advance of the LD cycle, old mice took significantly longer to reentrain their activity rhythm when compared with adult animals. Old mice also demonstrated a decline in the number of wheel revolutions per day and a tendency toward a decrease in the length of the active phase. An increase in fragmentation of activity across the 24-h day was obvious in aging animals, with bouts of activity being shorter and longer rest periods intervening between them. No age difference was detected in the maximum intensity of wheel-running activity. In DD, the free-running period was significantly longer in old mice compared with adults. In view of the rapidly expanding importance of the laboratory mouse for molecular and genetic studies of the mammalian nervous system, the present results provide a basis at the phenotypic level to begin to apply genetic methods to the analysis of circadian rhythms and aging in mammals.

Melatonin and activity rhythm responses to light pulses in mice with the Clock mutation

2003 ◽  
Vol 284 (5) ◽  
pp. R1231-R1240 ◽  
Author(s):  
David J. Kennaway ◽  
Athena Voultsios ◽  
Tamara J. Varcoe ◽  
Robert W. Moyer
Keyword(s):  
Wheel Running ◽  
Activity Rhythm ◽  
Mutant Mice ◽  
Constant Darkness ◽  
Wild Type ◽  
Continuous Darkness ◽  
Light Pulses ◽  
Essentially Normal ◽  
Running Activity ◽  
Wheel Running Activity

Melatonin and wheel-running rhythmicity and the effects of acute and chronic light pulses on these rhythms were studied in Clock Δ19 mutant mice selectively bred to synthesize melatonin. Homozygous melatonin-proficient Clock Δ19 mutant mice ( Clock Δ19/Δ19 -MEL) produced melatonin rhythmically, with peak production 2 h later than the wild-type controls (i.e., just before lights on). By contrast, the time of onset of wheel-running activity occurred within a 20-min period around lights off, irrespective of the genotype. Melatonin production in the mutants spontaneously decreased within 1 h of the expected time of lights on. On placement of the mice in continuous darkness, the melatonin rhythm persisted, and the peak occurred 2 h later in each cycle over the first two cycles, consistent with the endogenous period of the mutant. This contrasted with the onset of wheel-running activity, which did not shift for several days in constant darkness. A light pulse around the time of expected lights on followed by constant darkness reduced the expected 2-h delay of the melatonin peak of the mutants to ∼1 h and advanced the time of the melatonin peak in the wild-type mice. When the Clock Δ19/Δ19 -MEL mice were maintained in a skeleton photoperiod of daily 15-min light pulses, a higher proportion entrained to the schedule (57%) than melatonin-deficient mutants (9%). These results provide compelling evidence that mice with the Clock Δ19 mutation express essentially normal rhythmicity, albeit with an underlying endogenous period of 26–27 h, and they can be entrained by brief exposure to light. They also raise important questions about the role of Clock in rhythmicity and the usefulness of monitoring behavioral rhythms compared with hormonal rhythms.

Genetic analysis of daily physical activity using a mouse chromosome substitution strain

2009 ◽  
Vol 39 (1) ◽  
pp. 47-55 ◽  
Author(s):  
He S. Yang ◽  
Martha H. Vitaterna ◽  
Aaron D. Laposky ◽  
Kazuhiro Shimomura ◽  
Fred W. Turek
Keyword(s):  
Physical Activity ◽  
Physical Activity Level ◽  
Wheel Running ◽  
Daily Physical Activity ◽  
Activity Level ◽  
Constant Darkness ◽  
Circadian Period ◽  
Chromosome 13 ◽  
Running Activity ◽  
Wheel Running Activity

There is considerable evidence for a genetic basis underlying individual differences in spontaneous physical activity in humans and animals. Previous publications indicate that the physical activity level and pattern vary among inbred strains of mice and identified a genomic region on chromosome 13 as quantitative trait loci (QTL) for physical activity. To confirm and further characterize the role of chromosome 13 in regulating daily physical activity level and pattern, we conducted a comprehensive phenotypic study in the chromosome 13 substitution strain (CSS-13) in which the individual chromosome 13 from the A/J strain was substituted into an otherwise complete C57BL/6J (B6) genome. The B6 and A/J parental strains exhibited pronounced differences in daily physical activity, sleep-wake structure, circadian period and body weight. Here we report that a single A/J chromosome 13 in the context of a B6 genetic background conferred a profound reduction in both total cage activity and wheel-running activity under a 14:10-h light-dark cycle, as well as in constant darkness, compared with B6 controls. Additionally, CSS-13 mice differed from B6 controls in the diurnal distribution of activity and the day-to-day variability in activity onset. We further performed a linkage analysis and mapped a significant QTL on chromosome 13 regulating the daily wheel running activity level in mice. Taken together, our findings indicate a QTL on chromosome 13 with dramatic and specific effects on daily voluntary physical activity, but not on circadian period, sleep, or other aspects of activity that are different between B6 and A/J strains.

Activity rhythm of golden hamster (Mesocricetus auratus) can be entrained to a 19-h light-dark cycle

2005 ◽  
Vol 289 (4) ◽  
pp. R998-R1005 ◽  
Author(s):  
Juan J. Chiesa ◽  
Montserrat Anglès-Pujolràs ◽  
Antoni Díez-Noguera ◽  
Trinitat Cambras
Keyword(s):  
Golden Hamster ◽  
Wheel Running ◽  
Activity Rhythm ◽  
Mesocricetus Auratus ◽  
Precise Determination ◽  
Dark Cycle ◽  
Running Wheel ◽  
Running Activity ◽  
Wheel Running Activity

Both temporary access to a running wheel and temporary exposure to light systematically influence the phase producing entrainment of the circadian activity rhythm in the golden hamster ( Mesocricetus auratus). However, precise determination of entrainment limits remains methodologically difficult, because such calculations may be influenced by varying experimental paradigms. In this study, effects on the entrainment of the activity pattern during successive light-dark (LD) cycles of stepwise decreasing periods, as well as wheel running activity, were investigated. In particular, the hamster activity rhythm under LD cycles with a period (T) shorter than 22 h was studied, i.e., when the LD cycle itself had been shown to be an insufficiently strong zeitgeber to synchronize activity rhythms. Indeed, it was confirmed that animals without a wheel do not entrain under 11:11-h LD cycles (T = 22 h). Subsequently providing hamsters continuous access to a running wheel established entrainment to T = 22 h. Moreover, this paradigm underwent further reductions of the T period to T = 19.6 h without loss of entrainment. Furthermore, restricting access to the wheel did not result in loss of entrainment, while even entrainment to T = 19 h was observed. To explain this observed shift in the lower entrainment limit, our speculation centers on changes in pacemaker response facilitated by stepwise changes of T spaced very far apart, thus allowing time for adaptation.

Sex differences in the circadian control of hamster wheel-running activity

1983 ◽  
Vol 244 (1) ◽  
pp. R93-R105 ◽  
Author(s):  
F. C. Davis ◽  
J. M. Darrow ◽  
M. Menaker
Keyword(s):  
Sex Differences ◽  
Sex Difference ◽  
Wheel Running ◽  
Phase Shifts ◽  
Light Cycle ◽  
Dark Cycle ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Activity Onset ◽  
Males And Females

The circadian pacemaker that underlies the wheel-running activity of hamsters was studied in males and females. Sex differences were found in the mechanism by which the pacemaker entrains to light-dark cycles and in the timing of activity onset. When exposed to a light-dark cycle with a period of 24.75 h (with 1 h of light/cycle), males show a greater ability to maintain entrainment than do females. This difference in the upper limit of entrainment appears due to a sex difference in the magnitude of light-induced phase shifts. A small difference in free-running period may also contribute to the sex difference in entrainment. Two weeks after castration of adults, the sex difference in entrainment is not affected, indicating that the difference does not depend on circulating gonadal steroids or on estrous cyclicity of the female. However, castration of females at an early age increases their ability to entrain, whereas long-term castration of males seems to reduce entrainment ability. During entrainment to a 24-h light-dark cycle (LD 14:10), females were found to begin their daily activity before males and before castrated females. This difference is consistent with a sex difference in the magnitude of light-induced phase shifts and in entrainment of the pacemaker. However, evidence is given that the sex difference in activity onset might also be caused by a sex difference in the relationship of locomotor activity to the pacemaker in intact males and females.

P.1.d.019 Circadian pattern of wheel running activity of four laboratory mouse strains

2010 ◽  
Vol 20 ◽  
pp. S284
Author(s):  
M. Ágoston ◽  
J. Wellmann ◽  
P. Delagrange ◽  
M. Spedding ◽  
I. Gacsályi ◽  
...  
Keyword(s):  
Wheel Running ◽  
Laboratory Mouse ◽  
Mouse Strains ◽  
Circadian Pattern ◽  
Running Activity ◽  
Wheel Running Activity

scholarly journals Age-related changes in circadian responses to dark pulses

2000 ◽  
Vol 279 (2) ◽  
pp. R586-R590 ◽  
Author(s):  
Marilyn J. Duncan ◽  
Anthony W. Deveraux
Keyword(s):  
Wheel Running ◽  
Activity Rhythm ◽  
Circadian Pacemaker ◽  
Running Activity ◽  
Age Related ◽  
Wheel Running Activity ◽  
Significant Difference ◽  
Time Signals ◽  
Dark Pulse ◽  
Age Related Changes

Aging involves many alterations in circadian rhythms, including a loss of sensitivity to both photic and nonphotic time signals. This study investigated the sensitivity of young and old hamsters to the phase advancing effect of a 6-h dark pulse on the locomotor activity rhythm. Each hamster was tested four times during a period of ∼9 mo; periods of exposure to a 14-h photoperiod were alternated with the periods of exposure to constant light (20–80 lx), during which the dark pulses were administered. There was no significant difference in the phase shifts exhibited by the young (4–10 mo) and old hamsters (19–25 mo) or in the amount of wheel running activity displayed during each dark pulse. However, young hamsters had a significantly greater propensity to exhibit split rhythms immediately after the dark pulses. These results suggest that, although aging does not reduce the sensitivity of the circadian pacemaker to this nonphotic signal, it alters one property of the pacemaker, i.e., the flexibility of the coupling of its component oscillators.

scholarly journals Altered circadian activity and sleep/wake rhythms in the stable tubule only polypeptide (STOP) null mouse model of schizophrenia

SLEEP ◽  
2020 ◽  
Author(s):  
Samuel Deurveilher ◽  
Kristin Robin Ko ◽  
Brock St C Saumure ◽  
George S Robertson ◽  
Benjamin Rusak ◽  
...  
Keyword(s):  
Wheel Running ◽  
Active Phase ◽  
Null Mouse ◽  
Wild Type ◽  
Activity Rhythms ◽  
Lighting Conditions ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Lower Amplitude ◽  
Free Running

Abstract Sleep and circadian rhythm disruptions commonly occur in individuals with schizophrenia. Stable tubule only polypeptide (STOP) knockout (KO) mice show behavioral impairments resembling symptoms of schizophrenia. We previously reported that STOP KO mice slept less and had more fragmented sleep and waking than wild-type littermates under a light/dark (LD) cycle. Here, we assessed the circadian phenotype of male STOP KO mice by examining wheel-running activity rhythms and EEG/EMG-defined sleep/wake states under both LD and constant darkness (DD) conditions. Wheel-running activity rhythms in KO and wild-type mice were similarly entrained in LD, and had similar free-running periods in DD. The phase delay shift in response to a light pulse given early in the active phase under DD was preserved in KO mice. KO mice had markedly lower activity levels, lower amplitude activity rhythms, less stable activity onsets, and more fragmented activity than wild-type mice in both lighting conditions. KO mice also spent more time awake and less time in rapid eye movement sleep (REMS) and non-REMS (NREMS) in both LD and DD conditions, with the decrease in NREMS concentrated in the active phase. KO mice also showed altered EEG features and higher amplitude rhythms in wake and NREMS (but not REMS) amounts in both lighting conditions, with a longer free-running period in DD, compared to wild-type mice. These results indicate that the STOP null mutation in mice altered the regulation of sleep/wake physiology and activity rhythm expression, but did not grossly disrupt circadian mechanisms.

Failure of pinealectomy or melatonin to alter circadian activity rhythm of the rat

1982 ◽  
Vol 242 (3) ◽  
pp. R261-R264 ◽  
Author(s):  
P. W. Cheung ◽  
C. E. McCormack
Keyword(s):  
Wheel Running ◽  
Activity Rhythm ◽  
Physiological Mechanism ◽  
Continuous Darkness ◽  
Running Activity ◽  
Melatonin Administration ◽  
Wheel Running Activity ◽  
Free Running ◽  
Dim Light ◽  
Free Running Period

These experiments were undertaken to determine if the pineal gland is involved in the physiological mechanism by which the rat alters its free-running period (tau) in response to changes in illuminance. Spontaneous wheel-running activity was recorded from pinealectomized or sham-operated female Charles River rats. The tau of running activity was determined in continuous darkness (DD) or in continuous dim light (LL). Pinealectomized rats and sham-operated rats lengthened their tau's to approximately the same extent when shifted from DD to LL and shortened their tau's when shifted back to DD. Continuous melatonin administration via Silastic capsules failed to alter tau of rats kept in dim LL. These results indicate that the pineal is not primarily involved in the mechanism by which the rat alters tau in response to changes in illuminance.

Aging and photoperiod affect entrainment and quantitative aspects of locomotor behavior in Syrian hamsters

1997 ◽  
Vol 272 (4) ◽  
pp. R1219-R1225 ◽  
Author(s):  
K. Scarbrough ◽  
S. Losee-Olson ◽  
E. P. Wallen ◽  
F. W. Turek
Keyword(s):  
Locomotor Activity ◽  
Wheel Running ◽  
Activity Rhythm ◽  
Age Groups ◽  
Temporal Distribution ◽  
Similar Rate ◽  
Middle Aged ◽  
Running Activity ◽  
Age Related ◽  
Wheel Running Activity

Aging affects the regulation of diurnal and circadian rhythmicity. We tested the hypothesis that the age-related difference in the phase angle of entrainment of the locomotor activity rhythm to a light-dark (LD) cycle would be greater under LD 6:18 than LD 14:10. We also analyzed changes in quantitative aspects of wheel-running behavior according to age group. Young (9-wk-old), middle-aged (11- to 12-mo-old), and old (15- to 17-mo-old) male golden hamsters were entrained to a 14:10 LD cycle followed by re-entrainment to a 6:18 LD cycle. Fourteen days after the start of locomotor recording in LD 14:10 and again after 27 days in LD 6:18, the phase of activity onset, the total number of wheel revolutions performed per day, the peak intensity of wheel-running activity, the duration of the active period, and the level of fragmentation of locomotor activity were quantitated. We also studied the temporal distribution of the largest bout of wheel-running activity among the age groups in both photoperiods. Short days induced testicular regression at a similar rate among young, middle-aged, and old hamsters. The data are discussed in terms of the effects of age on overall circadian organization in the seasonally changing environment.

scholarly journals The Dorsal Medial Habenula Minimally Impacts Circadian Regulation of Locomotor Activity and Sleep

2017 ◽  
Vol 32 (5) ◽  
pp. 444-455 ◽  
Author(s):  
Yun-Wei A. Hsu ◽  
Jennifer J. Gile ◽  
Jazmine G. Perez ◽  
Glenn Morton ◽  
Miriam Ben-Hamo ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Clock Genes ◽  
Wheel Running ◽  
Circadian System ◽  
Sleep Stages ◽  
Constant Darkness ◽  
Running Activity ◽  
Medial Habenula ◽  
Wheel Running Activity ◽  
Central Pacemaker

In nocturnal rodents, voluntary wheel-running activity (WRA) represents a self-reinforcing behavior. We have previously demonstrated that WRA is markedly reduced in mice with a region-specific deletion of the transcription factor Pou4f1 (Brn3a), which leads to an ablation of the dorsal medial habenula (dMHb). The decrease in WRA in these dMHb-lesioned (dMHbCKO) mice suggests that the dMHb constitutes a critical center for conveying reinforcement by exercise. However, WRA also represents a prominent output of the circadian system, and the possibility remains that the dMHb is a source of input to the master circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus. To test this hypothesis, we assessed the integrity of the circadian system in dMHbCKO mice. Here we show that the developmental lesion of the dMHb reduces WRA under both a light-dark cycle and constant darkness, increases the circadian period of WRA, but has no effect on the circadian amplitude or period of home cage activity or the daily amplitude of sleep stages, suggesting that the lengthening of period is a result of the decreased WRA in the mutant mice. Polysomnographic sleep recordings show that dMHbCKO mice have an overall unaltered daily amplitude of sleep stages but have fragmented sleep and an overall increase in total rapid eye movement (REM) sleep. Photoresponsiveness is intact in dMHbCKO mice, but compared with control animals, they reentrain faster to a 6-h abrupt phase delay protocol. Circadian changes in WRA of dMHbCKO mice do not appear to emerge within the central pacemaker, as circadian expression of the clock genes Per1 and Per2 within the SCN is normal. We do find some evidence for fragmented sleep and an overall increase in total REM sleep, supporting a model in which the dMHb is part of the neural circuitry encoding motivation and involved in the manifestation of some of the symptoms of depression.

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