Effects of light intensity on the circadian temperature and feeding rhythms in the squirrel monkey

The circadian rhythms of body temperature and feeding appear to be timed by separate pacemakers. Tonic administration of light has been used to investigate the response of the pacemaker timing behavioral rhythms; however, the response of the body temperature rhythm has not been similarly examined. This study investigates the circadian timing of the body temperature rhythm under conditions of different light intensity. We simultaneously recorded the patterns of both feeding and body temperature in squirrel monkeys free-running in an environment free of external time cues. In each lighting condition, the periods of the body temperature and feeding rhythms were identical. In constant bright light the rhythm periods were longer than when the animals were exposed to constant dim light. In addition, the variability of the periods was dependent on light intensity. The feeding rhythm period variance of animals in constant bright light was smaller than when in dim light. Conversely, the period of the free-running body temperature rhythm exhibited more variability in bright light than in dim light. Further, in each condition, there were changes in phase angle relationship between feeding and body temperature which were qualitatively similar to those observed in humans, although quantitatively smaller in magnitude. Thus, in the squirrel monkey, tonic light studies reveal that the mean circadian period of the body temperature and feeding rhythms are similar. However, changes in phase relationship, and differential rhythm period stabilities suggest differences in the period of the underlying, tightly coupled pacemakers.     

Free‐running circadian period in adolescents and adults

Sleep timing shifts later during adolescence (second decade). This trend reverses at ~20 years and continues to shift earlier into adulthood. The current analysis examined the hypothesis that a longer free‐running circadian period during late adolescence (14–17 years) compared with adulthood (30–45 years) accounts for sleep timing differences. Sex and ancestry were also examined because previous reports find that women and those with African‐American ancestry have shorter free‐running periods. Circadian period was measured using an ultradian dark–light protocol (2 hr dark/sleep, 2 hr dim room light [~20 lux]/wake) over 3.4 days. Dim light melatonin onsets were measured before and after the ultradian protocol, from which the circadian period was derived. In contrast to our hypothesis, we found that free‐running circadian period was similar in adolescents and adults. African‐American adults had shorter free‐running circadian periods compared with adults of other ancestries. This ancestry difference was not seen in the adolescent group. Finally, we observed a non‐significant trend for shorter free‐running circadian periods in females compared with males. These data suggest that age‐related changes in circadian period after late adolescence do not account for sleep timing differences. These data provide further support for ancestry‐related differences in period, particularly in adults. Whether the large difference in circadian period between African‐American and other ancestries emerges later in development should be explored.     

Natural light exposure of young adults

Bright light has a role in natural coordination of mammalian circadian and seasonal rhythms. In humans, the light intensity must probably exceed 2000 lux to be optimal. Natural light exposures of 10 healthy adults were measured over a 24-hour period, using forehead illumination transducers connected to a portable computer. The subjects varied markedly in duration and timing of exposures to light greater than 2000 lux. On average, the subjects experienced bright light for only 90 minutes per day, less than the 3-8 hours of bright light necessary to maximally synchronize human circadian rhythms. These results suggest that natural and artificial light exposure for many Americans may be suboptimal for circadian and seasonal synchronization.     

Light responses of the circadian system in leptin deficient mice

Some evidences postulate a link between obesity and disturbances in circadian behavior. Here, we studied the manifestation of the circadian rhythm of motor activity and its response to light in the leptin deficiency model of obesity ob/ob mice. Motor activity in both ob/ob and wild type mice was first recorded in a small cage by activity meters with crossed infrared beams (IR) and later in a larger cage with a running wheel, where the number of wheel revolutions (WR) was also determined. Animals were maintained under light-dark (LD) or constant-dark (DD) conditions. We studied the free-running period and the rhythm profile, with special emphasis on the amount of activity in the dark and light phases of the LD cycle, and the phase and period responses to a light pulse. The results showed that ob/ob mice have a strong ultradian, rather than a circadian pattern, whose period range between 3 and 4.8 h. Also, these animals showed a percentage of activity during light higher than controls. We did not find differences in the endogenous period of the circadian rhythm between mice groups in DD. However, ob/ob mice showed stronger phase delays after a light pulse at ZT15 than controls, and less masking effects in the transition from LD to DD compared with controls. This suggests a weaker circadian pacemaker of the ob/ob mice compared with controls.     

Low amplitude entrainment of mice and the impact of circadian phase on behavior tests

A tremendous increase in the use of genetically engineered mice as experimental animals has led to increased scrutiny of mouse models generally and mouse behavioral paradigms specifically. Although mice are nocturnal, for practical reasons, most experimental procedures, including behavioral studies, are conducted during their inactive, sleep phase. Accumulating evidence indicates that myriad behavioral, cellular and biochemical processes fluctuate with circadian rhythmicity; however, time of day at which experiments are conducted is rarely controlled. The impact of circadian phase on the reliability of experimental results has received little attention and the present data are conflicting. This study addressed two questions. First, will laboratory mice in a typical animal care facility entrain to a low amplitude light cycle using bright/dim rather than light/dark cycles? A positive answer will make reversing photocycle easy to implement in any facility as dim light suitable for animal husbandry and behavioral testing can substitute for darkness during work hours. By monitoring home cage wheel running, we examined the effectiveness of a dim/bright photocycle as a zeitgeiber. We found that mice subjected to dim/bright photocycles effectively entrained such that their subjective night and activity onset coincided with the beginning of the dim light period, suggesting a potential strategy for standardization and management of circadian phase in nocturnal animals. In a second experiment, we asked what effect circadian phase has on behavioral performance in commonly used mouse behavioral tests. We found no main effect of circadian phase on outcome in open field activity, elevated plus maze emotionality, water maze spatial memory, novel object exploration and hyperactivity in response to amphetamine; however, we observed occasional interactions between circadian phase and both strain and sex that were neither consistent nor systematic. These data suggest that the tests examined here are relatively impervious to circadian phase. In general, testing mice during their active phase is more suitable for behavioral studies; a reversed dim/bright photocycle potentially offers one practical strategy for managing rodents' circadian cycles.     

Bright light treatment used for adaptation to night work and re-adaptation back to day life. A field study at an oil platform in the North Sea

Night workers complain of sleepiness, reduced performance and disturbed sleep due to lack of adjustment of the circadian rhythm. In simulated night-work experiments scheduled exposure to bright light has been shown to reduce these complaints. Here we studied the effects of bright light treatment on the adaptation to 14 days of consecutive night work at an oil platform in the North Sea, and the subsequent readaptation to day life at home, using the Karolinska sleep/wake diary. Bright light treatment of 30 min per exposure was applied during the first 4 nights of the night-shift period and the first 4 days at home following the shift period. The bright light exposure was scheduled individually to phase delay the circadian rhythm. Bright light treatment modestly facilitated the subjective adaptation to night work, but the positive effect of bright light was especially pronounced during the re-adaptation back to day life following the return home. Sleepiness was reduced and the quality of day was rated better after exposure to bright light. The modest effect of bright light at the platform was, possibly, related to the finding that the workers seemed to adapt to night work within a few days even without bright light. These results suggest that short-term bright light treatment may help the adaptation to an extended night-work period, and especially the subsequent re-adaptation to day life.     

Entrainment of the rat motor activity rhythm: effects of the light-dark cycle and physical exercise

The circadian system is believed to be composed of a population of oscillators that couple together and generate a single rhythm. If this coupling is not strong enough, the circadian system can be dissociated into two or more groups of oscillators, and this is manifested in a dissociation of the overt rhythm into at least two circadian components. This study aims to examine the influence of factors, such as the difference in impact between T and tau, light intensity, and access to a running wheel, on the distribution of motor activity throughout the light-dark (LD) cycle and the dissociation of the rhythm. Rats were submitted to LD cycles of 23 h (T23) or 25 h. For each such cycle, half the rats were submitted to high light intensity and the other half to low light intensity. For each of these conditions, half the rats were kept in small cages, and the other half were in cages with a running wheel. Rats were maintained first under LD cycles and afterwards under constant darkness (DD). Motor activity was recorded throughout the whole experiment by means of activity meters with infrared beams. Results show that the distribution of motor activity throughout the cycle and the after effects observed in the rhythm under DD depended on light intensity and access to the wheel. Moreover, under T23, some rats showed two simultaneous circadian components whose manifestation also depended on the experimental conditions. The results indicate that the strength of circadian entrainment to LD cycles in the rat depends on three factors: the period length of the LD cycle, light intensity used during the light phase, and access to a running wheel.     

Complex effects of melatonin: evidence for photoperiodic responses in humans?

The primary function of melatonin in mammals is to convey information about the changing length of the night in the course of the year. This information is used by photoperiodic species to ensure the correct timing of seasonally variable functions such as reproduction, coat growth, and probably the duration and organization of sleep. Melatonin appears not to be essential for circadian organization but reinforces functions associated with darkness. In diurnal humans this of course includes sleep and lowered body temperature. It may act as an adjunct to light for the maintenance of synchrony with the solar day. Exogenous melatonin can both advance and delay the timing of sleep and other circadian functions and appears to stabilize sleep to a 24 h period taken daily at an appropriate time in free running conditions. However, there is as yet little evidence that it can consistently synchronize free running strongly endogenous variables such as core temperature. Its effects on sleep in free run are complex, depend on circadian time of administration, and can in part be interpreted on a photoperiodic basis.     

Bright light affects human circadian rhythms

The relative effectiveness of external zeitgebers synchronizing circadian rhythms can be evaluated by mesuring the size of the range of entrainment. The experimental approach to measure entrainment limits is the application of an artificial zeitgeber with slowly and steadily changing period. In human circadian rhythms, an absolute light-dark (LD) cycle with a light intensity during L of 100 lux or less, results in an upper entrainment limit of 26.91±0.24 hours. The same limit is reached in constant illumination when only informations are given to the subjects. Consequently, the LD cycle is effective mainly with its behavioral component characterized by the request of the light-dark alternation to go to rest. In experiments with the same experimental protocol but higher intensity of illumination during L (400 lux, i.e., exceeding the threshold beyond which melatonin excretion is suppressed in humans), human circadian rhythms can be synchronized within a much larger range; the upper entrainment limit is, with all overt rhythms measured, beyond 29 hours. This means that bright light has an effect on the human circadian system which is qualitatively different from that of dim light, and which is similar to the effect of light in most animal experiments. This finding has theoretical and practical implications.     

Use of bright light to treat maladaptation to night shift work and circadian rhythm sleep disorders

SUMMARY  Night work is associated with increased sleepiness and disturbed sleep. Maladaptation of the circadian system, which is phase-adjusted to day time work and thus promotes sleepiness during its nadir at night and wakefulness (or disturbed sleep) during the day, contributes substantially to this problem. A major cause of suboptimal circadian phase adjustment among night workers is the exposure to morning light, which prevents the delay needed for optimal adjustment to night work. Several laboratory studies indicate that careful application of bright light may cause the circadian system to shift to any desired phase. Furthermore, studies of simulated night work demonstrate that night exposure to bright light can virtually eliminate circadian maladjustment among night workers. While the results are promising, there is still, however, an urgent need for longitudinal studies of bright light application in. real-life settings.     

Use of running wheels regulates the effects of the ovaries on circadian rhythms.

Free-running circadian rhythms in core temperature, wheel-running and general locomotor activity were studied in ovariectomized or intact female rats housed with or without access to a running wheel. No differences in the monitored parameters were found between the intact and ovariectomized rats without a wheel. In the presence of a wheel, however, the intact rats differed from those that had been ovariectomized by displaying a shorter circadian period, an increased amplitude of the temperature rhythm, and strikingly higher rates of wheel-running and general locomotor activity. After estradiol treatment, the ovariectomized rats with a wheel developed a small increase in the temperature amplitude, and also in the correlation between wheel-running and general locomotor activity; these changes were not associated with a significant increase in wheel-running or a shortening of the circadian period. We conclude that some of the differences in circadian function between intact and ovariectomized rats are due to the differential use they make of running wheels, when available, and not directly attributable to the absence or presence of gonadal steroids.     

Sleep propensity and sleep architecture after bright light exposure at three different times of day

SUMMARY  The aim of this work was to study the effects of bright light-induced circadian phase shifts on sleep propensity and sleep architecture while the timing of the sleep/wake cycle is kept constant. Twenty-three normal subjects underwent an 11-day study including: (i) baseline sleep and vigilance evaluation; (ii) baseline evaluation of the circadian temperature rhythm with a 40-h constant routine; (iii) five hours of bright light exposure on each of three days; (iv) post-treatment sleep and vigilance evaluation; (v) post-treatment circadian rhythm evaluation with a second 40-h constant routine. Subjects were divided into three groups: eight subjects were exposed to bright light in the morning ('Morning group'), eight subjects were exposed in the evening ('Evening group'), and seven subjects were exposed in the afternoon ('Afternoon group'). After light exposure, the Morning group showed an advance of 1.23 h in the phase of the temperature rhythm, the Evening group showed a delay of 1.62 h, and the Afternoon group showed a non-significant advance of 0.5 h. In support of expectations, early-night sleep propensity was decreased by evening bright light, was increased in almost all subjects exposed to morning bright light, and was not changed by afternoon bright light exposure. The phase shift created by bright light exposure did not seem to be large enough to have a systematic effect on sleep consolidation or on REM sleep parameters in any of the three groups, suggesting that these variables are less sensitive to alterations in phase of the circadian oscillator than early-night sleep propensity.     

Circadian rhythmicity and behavioral depression: I. Effects of stress

Rats were exposed to repeated sessions of inescapable footshock, and behavioral depression was subsequently assessed by measuring escape performance during exposure to escapable shock in a different testing environment. Free-running circadian activity rhythms were assessed using running wheels for approximately three weeks before and after administration of inescapable shock. Several animals showed lengthening of free-running period and decreases in activity level following shock. Similar effects were also seen in rats that were removed from their running wheels, placed within the shock apparatus, and not given shock, but not in nonhandled control animals. Furthermore, period lengthening in shocked and handled rats was positively correlated with escape performance, suggesting that circadian rhythm alterations occurred in those animals that were best able to cope with shock or handling-related stressors. In contrast, individual differences in circadian period and activity level during baseline conditions were not predictive of either escape performance or circadian rhythm alterations. These results suggest that successful behavioral adaptation to stress may be associated with alterations of circadian rhythmicity.     

Evening ambient light exposure can reduce circadian phase advances to morning light independent of sleep deprivation

Short sleep/dark durations are common in modern society. We investigated if exposure to additional evening ambient light, often associated with later bedtimes and short sleep, reduces circadian phase advances to morning bright light. Twelve healthy subjects participated in two conditions that differed in the distribution of sleep before exposure to morning bright light. Subjects had a consolidated 9‐h night time sleep opportunity, or a 3‐h daytime nap followed by a 6‐h night time sleep opportunity, each before morning bright light. Eight of the 12 subjects obtained similar amounts of sleep in both conditions, and yet still showed significant reductions in phase advances with 6‐h nights (1.7 versus 0.7 h, P < 0.05). These results suggest that the exposure to additional evening ambient light often associated with short sleep episodes can significantly reduce phase advances to morning light, and may therefore increase the risk for circadian misalignment.     

Circadian rhythm of core body temperature in two laboratory mouse lines

The circadian rhythm of core body temperature (Tb) was examined in two mouse lines bidirectionally selected for nest-building behavior (small (SNB) and big nest-builders (BNB)). This selection also resulted in more robust circadian organization of wheel-running activity in the SNB compared to the BNB mice. Tb was measured by an e-mitter implanted in the abdominal cavity. The circadian Tb rhythm of the SNB was more robust compared to the BNB regardless of whether the animals had access to a running wheel or not and regardless of the lighting conditions, i.e., 12 h:12 h light:dark (LD) cycle or constant dark (DD). Wheel-running activity rhythms of SNB were more robust in LD and DD compared to BNB. The amplitude of the circadian Tb rhythm increased significantly in response to wheel access in both mouse lines, but was not significantly different between the BNB and SNB. However, BNB tended to have lower amplitudes of circadian Tb rhythm in the absence of running wheels and a larger increase in the amplitude upon access to a running wheel compared to SNB. No differences were found in LD and DD between the lines in mean Tb and wheel-running activity levels. In addition, no differences between the two mouse lines were found in the free-running period of the Tb or wheel-running activity rhythms in DD. Overall, our findings reveal a more robust circadian phenotype of the SNB compared to the BNB.     

Circadian rhythms of locomotor activity in the squirrel monkey, Saimiri sciureus, under conditions of self-controlled light-dark cycles.

Locomotor activity was recorded from three squirrel monkeys, Saimiri sciureus, housed singly in cages inside a sound-proof chamber. Each animal was exposed twice to each of three conditions; continuous dim illumination (dim LL), continuous bright illumination (bright LL), and conditions in which the animal could turn on bright light by itself (self-controlled light-dark cycle: LDs). The mean circadian period, tau, the activity time, alpha, and the amount of activity, A, were computed for each single condition. It was found that, in LL, tau, alpha and A were positively correlated with the intensity of illumination. In LDs, tau was longer and A larger than in either dim or bright LL. The lengthening of tau in squirrel monkeys by a self-controlled light-dark cycle is compared with similar findings in birds and man, and is discussed in view of the observation that the tau-characteristics of diurnal mammals deviate from those known from other diurnal species of vertebrates.     

Circadian clock resetting by behavioral arousal: neural correlates in the midbrain raphe nuclei and locus coeruleus

Some procedures for stimulating arousal in the usual daily rest period (e.g., gentle handling, novel wheel-induced running) can phase shift circadian rhythms in Syrian hamsters, while other arousal procedures are ineffective (inescapable stress, caffeine, modafinil). The dorsal and median raphe nuclei (DRN, MnR) have been implicated in clock resetting by arousal and, in rats and mice, exhibit strong regionally specific responses to inescapable stress and anxiogenic drugs. To examine a possible role for the midbrain raphe nuclei in the differential effects of arousal procedures on circadian rhythms, hamsters were aroused for 3 h in the mid-rest period by confinement to a novel running wheel, gentle handling (with minimal activity) or physical restraint (with intermittent, loud compressed air stimulation) and sacrificed immediately thereafter. Regional expression of c-fos and tryptophan hydroxylase (TrpOH) were quantified immunocytochemically in the DRN, MnR and locus coeruleus (LC). Neither gentle handling nor wheel running had a large impact on c-fos expression in these areas, although the manipulations were associated with a small increase in c-Fos in TrpOH-like and TrpOH-negative cells, respectively, in the caudal interfascicular DRN region. By contrast, restraint stress significantly increased c-Fos in both TrpOH-like and TrpOH-negative cells in the rostral DRN and LC. c-Fos-positive cells in the DRN did not express tyrosine hydroxylase. These results reveal regionally specific monoaminergic correlates of arousal-induced circadian clock resetting, and suggest a hypothesis that strong activation of some DRN and LC neurons by inescapable stress may oppose clock resetting in response to arousal during the daily sleep period. More generally, these results complement evidence from other rodent species for functional topographic organization of the DRN.     

Control of behavioral circadian rhythms for nesting and wheel running in mice

In Experiment 1 a circadian rhythm for nest-building behavior is demonstrated in 10 males from a genetically heterogeneous stock of Mus musculus. In Experiment 2, this circadian rhythm in nesting and that for wheel running activity were monitored simultaneously in an additional sample of five males from the same stock. Under a 16:8 LD photoperiod, mice displayed a 24-hr periodicity for both behaviors but a phase difference in peak behavioral intensities of approximately two and one-half hours. After ten days of exposure to constant light both rhythms persisted, but with no detectable difference in phase. The altered phase relationship under constant light suggests a difference in control of the circadian periodicities of these two behaviors. In Experiment 3, 5 additional males were subjected to a 10-hr shift in photoperiod to further examine control of these rhythms as well as those in food and water consumption. All four circadian rhythms re-entrained within four days. Thus, their entrainment mechanisms are functionally similar in spite of the differences in control suggested in Experiment 2.     

Free-running circadian rhythms of muscle strength, reaction time, and body temperature in totally blind people

Light is the major synchronizer of circadian rhythms. In the absence of light, as for totally blind people, some variables, such as body temperature, have an endogenous period that is longer than 24 h and tend to be free running. However, the circadian rhythm of muscle strength and reaction time in totally blind people has not been defined in the literature. The objective of this study was to determine the period of the endogenous circadian rhythm of the isometric and isokinetic contraction strength and simple reaction time of totally blind people. The study included six totally blind people with free-running circadian rhythms and four sighted people (control group). Although the control group required only a single session to determine the circadian rhythm, the blind people required three sessions to determine the endogenous period. In each session, isometric strength, isokinetic strength, reaction time, and body temperature were collected six different times a day with an interval of at least 8 h. The control group had better performance for strength and reaction time in the afternoon. For the blind, this performance became delayed throughout the day. Therefore, we conclude that the circadian rhythms of strength and simple reaction time of totally blind people are within their free-running periods. For some professionals, like the blind paralympic athletes, activities that require large physiological capacities in which the maximum stimulus should match the ideal time of competition may result in the blind athletes falling short of their expected performance under this free-running condition.     

Circadian rhythms of activity and drinking in mice lacking angiotensin II 1A receptors.

Angiotensin II (ANG II) type 1 receptors are found in the mouse suprachiasmatic nucleus (SCN), the site of the circadian pacemaker, but their significance for circadian timekeeping is unknown. We examined circadian rhythms of wheel running and drinking in angiotensin AT(1a) receptor knockout (KO) mice. Mean daily running and drinking activity were elevated in KO mice under a light-dark (LD) cycle and in constant dark (DD). These increases were confined to the usual active (dark) period, thus, the 'amplitude' of running and drinking rhythms was higher in KO mice. The phase of entrainment to LD (measured by the onset of the daily active period) did not differ between groups, either in LD or on the first day of DD ('unmasked' phase). KO mice showed a modestly shorter free-running period (tau) in DD. The direction and magnitude of phase shifts to light pulses at two circadian times (CTs) in DD did not differ between groups. Core functions of the circadian system appear intact following AT(1a) receptor KO. The modestly shorter tau and increased rhythm amplitude in KO mice may be secondary to an effect of the mutation on the level of running and drinking activity.