The Food-entrainable Oscillator Is a Complex of Non-SCN Activity Bout Oscillators Uncoupled From the SCN Circadian Pacemaker

2021 ◽  
pp. 074873042110479
Author(s):  
Shinya Nishide ◽  
Yohko Suzuki ◽  
Daisuke Ono ◽  
Sato Honma ◽  
Ken-ichi Honma
Keyword(s):  
Clock Genes ◽  
Wheel Running ◽  
Core Body Temperature ◽  
Circadian Pacemaker ◽  
Loss Mechanism ◽  
Peripheral Tissues ◽  
Daily Feeding ◽  
Activity Peak ◽  
Running Activity ◽  
Wheel Running Activity

The food-entrainable oscillator, which underlies the prefeeding activity peak developed by restricted daily feeding (RF) in rodents, does not depend on the circadian pacemaker in the suprachiasmatic nucleus (SCN) or on the known clock genes. In the present study, to clarify the roles of SCN circadian pacemaker and nutrient conditions on the development of prefeeding activity peak, RF of 3-h daily feeding was imposed on four groups of adult male mice for 10 cycles at different circadian times, zeitgeber time (ZT)2, ZT8, ZT14, and ZT20, where ZT0 is the time of lights-on in LD12:12. Seven days after the termination of RF session with ad libitum feeding in between, total food deprivation (FD) for 72 h was imposed. Wheel-running activity and core body temperature were measured throughout the experiment. Immediately after the RF or FD session, the PER2::LUC rhythms were measured in the cultured SCN slices and peripheral tissues. Not only the buildup process and magnitude of the prefeeding activity peak, but also the percentages of nocturnal activity and hypothermia developed under RF were significantly different among the four groups, indicating the involvement of light entrained circadian pacemaker. The buildup of prefeeding activity peak was accomplished by either phase-advance or phase-delay shifts (or both) of activity bouts comprising a nocturnal band. Hypothermia under FD was less prominent in RF-exposed mice than in naïve counterparts, indicating that restricted feeding increases tolerance to caloric restriction as well as to the heat loss mechanism. RF phase-shifted the peripheral clocks but FD did not affect the clocks in any tissue examined. These findings are better understood by assuming multiple bout oscillators, which are located outside the SCN and directly drive activity bouts uncoupled from the circadian pacemaker by RF or hypothermia.

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.

Stability of circadian timing with age in Syrian hamsters

1998 ◽  
Vol 275 (4) ◽  
pp. R960-R968 ◽  
Author(s):  
Fred C. Davis ◽  
N. Viswanathan
Keyword(s):  
Wheel Running ◽  
Activity Level ◽  
Circadian Pacemaker ◽  
Experimental Conditions ◽  
Syrian Hamsters ◽  
Running Activity ◽  
Age Related ◽  
Wheel Running Activity ◽  
Free Running ◽  
Free Running Period

The causes of age-related disruptions in the timing of human sleep and wakefulness are not known but may include changes in both the homeostatic and circadian regulation of sleep. In Syrian hamsters the free running period of the circadian activity/rest rhythm has been reported to shorten with age. Although this has been observed under a variety of experimental conditions, the changes have been small and their consistency uncertain. In the present study, the wheel running activity/rest rhythm was continuously measured in male Syrian hamsters ( Mesocricetus auratus) in dim constant light (<1 lx) from 8 wk of age until death. Fifteen hamsters survived to at least 90 wk (28%). The average free running period of these hamsters did not change with age. In 18 hamsters that died between 50 and 88 wk, free running period also did not change before death. In contrast to free running period, other measures related to activity level changed significantly with age and before death. Despite changes in the expression of the activity/rest rhythm, the free running period of the hamster circadian pacemaker remained remarkably stable with age.

Temporal phasing of locomotor activity, heart rate rhythmicity, and core body temperature is disrupted in VIP receptor 2-deficient mice

2011 ◽  
Vol 300 (3) ◽  
pp. R519-R530 ◽  
Author(s):  
Jens Hannibal ◽  
Hansen M. Hsiung ◽  
Jan Fahrenkrug
Keyword(s):  
Heart Rate ◽  
Locomotor Activity ◽  
Body Temperature ◽  
Circadian Rhythms ◽  
Wheel Running ◽  
Core Body Temperature ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Core Body ◽  
Deficient Mice

Neurons of the brain's biological clock located in the hypothalamic suprachiasmatic nucleus (SCN) generate circadian rhythms of physiology (core body temperature, hormone secretion, locomotor activity, sleep/wake, and heart rate) with distinct temporal phasing when entrained by the light/dark (LD) cycle. The neuropeptide vasoactive intestinal polypetide (VIP) and its receptor (VPAC2) are highly expressed in the SCN. Recent studies indicate that VIPergic signaling plays an essential role in the maintenance of ongoing circadian rhythmicity by synchronizing SCN cells and by maintaining rhythmicity within individual neurons. To further increase the understanding of the role of VPAC2 signaling in circadian regulation, we implanted telemetric devices and simultaneously measured core body temperature, spontaneous activity, and heart rate in a strain of VPAC2-deficient mice and compared these observations with observations made from mice examined by wheel-running activity. The study demonstrates that VPAC2 signaling is necessary for a functional circadian clock driving locomotor activity, core body temperature, and heart rate rhythmicity, since VPAC2-deficient mice lose the rhythms in all three parameters when placed under constant conditions (of either light or darkness). Furthermore, although 24-h rhythms for three parameters are retained in VPAC2-deficient mice during the LD cycle, the temperature rhythm displays markedly altered time course and profile, rising earlier and peaking ∼4–6 h prior to that of wild-type mice. The use of telemetric devices to measure circadian locomotor activity, temperature, and heart rate, together with the classical determination of circadian rhythms of wheel-running activity, raises questions about how representative wheel-running activity may be of other behavioral parameters, especially when animals have altered circadian phenotype.

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.

Differential effects of food restriction on pituitary-testicular function in mice

1985 ◽  
Vol 248 (2) ◽  
pp. R181-R189 ◽  
Author(s):  
J. L. Blank ◽  
C. Desjardins
Keyword(s):  
Food Intake ◽  
Animal Models ◽  
Food Restriction ◽  
Wheel Running ◽  
Temporal Organization ◽  
Deer Mice ◽  
House Mice ◽  
Testicular Function ◽  
Running Activity ◽  
Wheel Running Activity

The reproductive responses of two species of wild rodents, house mice and deer mice, were evaluated following a 30% reduction in food intake for 5 wk. These animal models were chosen as prototypes of other rodent species because each employs unique functional adjustments when confronted with reduced resources in their natural habitats. Modest inanition failed to alter pituitary-testicular function in house mice; neither spermatogenesis nor plasma concentrations of luteinizing hormone (LH) and testosterone were modified. In sharp distinction, deer mice exposed to restricted food intake showed significant reductions in plasma LH and testosterone and an accompanying loss in spermatogenesis. Reduced food intake also caused pronounced shifts in the temporal organization and amount of wheel-running activity in both animal models, albeit in a dichotomous fashion. House mice exhibited the same amount of wheel-running activity throughout inanition, but the diel periodicity of locomotor behavior was shifted from the dark to the light period. Deer mice, in comparison, significantly curtailed wheel-running activity during the dark hours but ran in precise phase relationship with the light-dark cycle. Taken together, our results establish that the male reproductive system and its supporting neuroendocrine and behavioral correlates can be disrupted by modest levels of food restriction in certain animal models.

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.

scholarly journals Strain screen and haplotype association mapping of wheel running in inbred mouse strains

2010 ◽  
Vol 109 (3) ◽  
pp. 623-634 ◽  
Author(s):  
J. Timothy Lightfoot ◽  
Larry Leamy ◽  
Daniel Pomp ◽  
Michael J. Turner ◽  
Anthony A. Fodor ◽  
...  
Keyword(s):  
Physical Activity ◽  
Association Mapping ◽  
Wheel Running ◽  
Association Studies ◽  
Mouse Strains ◽  
Haplotype Association ◽  
Male And Female ◽  
Female Mice ◽  
Running Activity ◽  
Wheel Running Activity

Previous genetic association studies of physical activity, in both animal and human models, have been limited in number of subjects and genetically homozygous strains used as well as number of genomic markers available for analysis. Expansion of the available mouse physical activity strain screens and the recently published dense single-nucleotide polymorphism (SNP) map of the mouse genome (≈8.3 million SNPs) and associated statistical methods allowed us to construct a more generalizable map of the quantitative trait loci (QTL) associated with physical activity. Specifically, we measured wheel running activity in male and female mice (average age 9 wk) in 41 inbred strains and used activity data from 38 of these strains in a haplotype association mapping analysis to determine QTL associated with activity. As seen previously, there was a large range of activity patterns among the strains, with the highest and lowest strains differing significantly in daily distance run (27.4-fold), duration of activity (23.6-fold), and speed (2.9-fold). On a daily basis, female mice ran further (24%), longer (13%), and faster (11%). Twelve QTL were identified, with three (on Chr. 12, 18, and 19) in both male and female mice, five specific to males, and four specific to females. Eight of the 12 QTL, including the 3 general QTL found for both sexes, fell into intergenic areas. The results of this study further support the findings of a moderate to high heritability of physical activity and add general genomic areas applicable to a large number of mouse strains that can be further mined for candidate genes associated with regulation of physical activity. Additionally, results suggest that potential genetic mechanisms arising from traditional noncoding regions of the genome may be involved in regulation of physical activity.

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