Effects of restricted food access on circadian fluctuation of serotonin N-acetyltransferase activities in hereditary microphthalmic rats

The characteristics in diurnal fluctuation of serotonin N-acetyltransferase activity were examined in normal and microphthalmic mutant rats of the Donryu strain under ad lib or restricted feeding conditions. Under a 12:12-h light:dark (12-h LD) cycle with free access to food, normal-sighted rats exhibited typical nocturnal increases in the activity of pineal serotonin N-acetyltransferase, being more than 50-fold higher in the dark period than that in the light period, but hereditary blind rats showed nonperiodic change in the pineal enzyme activity in the average, suggesting that the rhythms in individuals have become free-running, asynchronous. When the subjective night or subjective day of the mutants was discerned by active or inactive in the locomotor activity, the pineal enzyme activities in the mutants increased at the subjective night but depressed at the subjective daytime. When food access was restricted only for 6 h in the light period of the LD cycle, normal rats still showed the nocturnal increases in the pineal enzyme activity, but hereditary blind rats manifested a blunt peak in the activity of the pineal enzyme at eating time in the light period. The results suggest that microphthalmic mutant rats maintain the ability to shift and to synchronize their circadian phases induced by restricted access to food, even if they completely lack their optic nerve and visual input to the circadian clock.     

Feeding cycles entrain circadian rhythms of locomotor activity in CS mice but not in C57BL/6J mice

The effects of periodic, restricted feeding (RF) for two hours at a fixed time of day on the circadian rhythms of locomotor activity were examined in CS and C57BL/6J mice, kept under continuous dim, red lights (LLdim). In C57BL/6J mice, free-running rhythms were not affected by an RF schedule, although anticipatory behavior prior to the food access period was observed. On the other hand, the free-running rhythms of CS mice did entrain to an RF schedule, exhibiting anticipatory behavior. The free-running rhythms of none of the control animals in either strain exhibited any effects resulting from the periodic disturbances occurring concurrently with the performance of RF. These results indicate that the circadian pacemaker couples with the food entrainable oscillator (FEO) in CS mice, but that such coupling may not exist, or may be very weak, in C57BL/6J mice.     

Food anticipatory activity and photic entrainment in food-restricted BALB/c mice

The BALB/c mouse was evaluated as a model for the study of entrainment of circadian rhythms by feeding schedules. Mice were housed in a 12:12-h light-dark (LD) environment with food available for 3-5 h/day (5 h before dark onset). Food anticipatory activity (FAA) rhythms were evident in all mice, ranging from robust in some to weak and variable in others. Advancing transients of the end of nocturnal activity were evident in many cases, culminating in a significant shortening of the main bout of nocturnal activity. Transients and contraction of nocturnal activity were not dependent on the expression of FAA. Following restricted feeding, nocturnal activity expanded by a series of delaying transients. On the first day of constant dark (DD) with ad libitum food access following restricted feeding in LD, the phase from which activity free-ran was advanced by comparison with control tests. Transients, compressed nocturnal activity, and advanced phase of free-run suggest that feeding schedules cause phase advancement of light-entrained rhythms in BALB/c mice. When restricted feeding was imposed in DD, several mice expressed robust FAA concurrent with a free-running activity component. In some cases, free-running rhythms entrained to feeding time, and in other cases, the period of the free run lengthened toward 24 h. These data show that restricted feeding in BALB/c mice can engage a circadian mechanism driving FAA rhythms and can also modulate the phase of photic entrainment, possibly by a direct entraining effect on the light-entrained rhythm. The BALB/c mouse strain, in several respects, appears to be a useful model for the study of scheduled feeding and circadian rhythms.     

Effects of restricted feeding schedules on circadian organization in squirrel monkeys

Free running circadian rhythms of motor activity, food-motivated lever-pressing, and either drinking (N = 7) or body temperature (N = 3) were recorded from 10 squirrel monkeys maintained in constant illumination with unlimited access to food. Food availability was then restricted to a single unsignaled 3-hour interval each day. The feeding schedule failed to entrain the activity rhythms of 8 monkeys, which continued to free-run. Drinking was almost completely synchronized by the schedule, while body temperature showed a feeding-induced rise superimposed on a free-running rhythm. Nonreinforced lever-pressing showed both a free-running component and a 24-hour component that anticipated the time of feeding. At the termination of the schedule, all recorded variables showed free-running rhythms, but in 3 animals the initial phase of the postschedule rhythms was advanced by several hours, suggesting relative coordination. Of the remaining 2 animals, one exhibited stable entrainment of all 3 recorded rhythms, while the other appeared to entrain temporarily to the feeding schedule. These results indicate that restricted feeding schedules are only a weak zeitgeber for the circadian pacemaker generating free-running rhythms in the squirrel monkey. Such schedules, however, may entrain a separate circadian system responsible for the timing of food-anticipatory changes in behavior and physiology.     

Restricted feeding and circadian activity rhythms of a predatory marsupial, Dasyuroides byrnei

There is considerable disagreement as to whether food availability entrains circadian activity rhythms in omnivorous laboratory rodents. However, in carnivorous mammals a restricted feeding regime could act as a zeitgeber because the predator should hold a periodism correlated to that of the prey. Nevertheless, a restricted feeding schedule does not dominate the LD cycle for entrainment of circadian activity rhythms of the nocturnal predator Dasyuroides byrnei, nor does it entrain the free-running activity rhythms in DD. Anticipatory wheel running prior to food availability was observed in most animals. Some evidence for weak coupling between LD-entrained and meal-associated oscillators was indicated by occurrences of relative coordination. This species does not appear to have a dominance hierarchy of zeitgebern different to that reported for laboratory rodents. One would have predicted that it would have been ecologically adaptive for cycles of food availability to be more important than the LD cycle in this species.     

The effects of restricted food access upon locomotor activity in rats with suprachiasmatic nucleus lesions

The purpose of the study was to investigate the ability of rats with suprachiasmatic nucleus (SCN) lesions to anticipate restricted food access (RFA). The sham operated controls demonstrated entrainment of locomotor activity to a LD 12:12 cycle with ad libitum food and water, while the lesioned animals were arrhythmic in their running behavior. When exposed to constant light (LL) and presentation of food once every 24 hours, anticipatory wheel running was observed in both groups. A return to ad lib food and the previous LD 12:12 schedule produced a slow re-entrainment of running in the controls and arrhythmic activity in the SCN animals. The results suggest that the SCN is not necessary for the appearance of locomotor rhythms in the rat.     

Food entrainment to 4-h T cycles in rats kept under constant lighting conditions.

The effect of 4-h feeding cycles on the feeding pattern of rats kept under constant light and constant darkness, was analysed. In both cases, the scheduled pattern of food-approach behavior elicited dissociation of the feeding activity into several components associated to the feeding times (CAFT), which coexisted with the previous circadian free-running rhythms. In LL rats and in the rest phase of DD animals, the CAFT was characterized by an increased number of food approaches confined exclusively to the period of food availability, with poor anticipatory activity. However, in the active phase of some DD rats, CAFT included an additional anticipatory activity. The interaction between the CAFT and the free-running rhythms involved modulation of the CAFT, depending on the free-running periodicity. After termination of the feeding-restriction schedule, some DD and LL animals retained the CAFT for at least 3 days. However, when the access to food was blocked 10 days after ending the restricted schedule, rats did not show any feeding activity associated to the previous feeding times. A spontaneous feeding pattern similar to that imposed by the previous feeding schedule emerged immediately after food deprivation in two of the DD animals. Although these results are compatible with the existence of a food-entrainable pacemaker, the existence of a multioscillatory light-entrainable pacemaker with some oscillators entrained by food pulses and others free-running may explain our results.     

Circadian rhythm of locomotor activity in the four-striped field mouse, Rhabdomys pumilio: a diurnal African rodent

Although humans are diurnal in behaviour, animal models used for the study of circadian rhythms are mainly restricted to nocturnal rodents. This study focussed on the circadian behaviour of a rodent from South Africa that has a preference for daylight, the four-striped field mouse, Rhabdomys pumilio. In order to characterise the behavioural pattern of daily activity, locomotor rhythms were studied under different light regimes using an automated data recording system. Under conditions of natural daylight, which include dawn and dusk transitions, R. pumilio exhibited activity restricted to the daytime period. Activity was concentrated around morning and evening with a decrease during mid-day. A similar diurnal preference pattern of behaviour was recorded under a light-dark cycle of artificial illumination. Under conditions of constant darkness, the four-striped field mouse exhibited a free-running circadian rhythm of locomotor activity with activity concentrated during the subjective day. Free-running rhythms varied greatly between individuals, from slightly less to slightly more than 24 h (range = 23.10 to 24.80 h). Under conditions of constant light, the mice were more active during subjective day, but the free-running rhythm in all individuals was consistently longer than 24 h (range = 24.30 to 24.79 h).     

Restricted feeding: a nonphotic zeitgeber in the rabbit.

The free-running circadian rhythms of five behavioral functions of the rabbit were masked by unsignalled restricted food access (RF). The rhythms were reorganized immediately, a large part of events being assembled around the end of food availability. In addition to masking a slower process of entrainment was running: a component of anticipatory activity (AA) was established 1-3 h before food access. AA consolidated in continuation of the camouflaged free-running rhythm. The time of AA establishment correlated significantly with the phase angle difference (PAD) between free-running rhythm and RF: it decreased with decreasing positive PAD. With the consolidation of AA, the rhythms had attained a stable phase relation to RF. At the termination of RF, the circadian rhythms started to free-run again, the phase being dependent from that of the preceding RF schedule. The period length of the RF zeitgeber (TRF) had some impact on tau of the circadian rhythm. This aftereffect was most evident after termination of TRF less than 24 h: the free-running rhythm continued for up to 49 days with a tau less than 24 h and turned longer thereafter. The results demonstrate the entrainment of circadian rhythms of the rabbit by RF in addition to masking.     

Estrous correlated modulations of circadian and ultradian wheel-running activity rhythms in LEW/Ztm rats

Estrogen treatment alters the expression of ultradian activity rhythms in male and female LEW/Ztm rats. This finding raises the possibility that the expression of ultradian rhythms may vary on different days of the estrous cycle. To test this hypothesis, we recorded the circadian and ultradian wheel-running activity rhythms of entrained (LD 12:12) and free-running sexually mature LEW/Ztm females during their 4- or 5-day estrous cycle. The mean daily activity, the duration of activity, the circadian period of activity, and the occurrence of ultradian rhythms differed significantly among the days of the estrous cycle. In LD 12:12, the phase angle difference between the beginning of activity and light offset varied reliably in 5-day cycling animals. The highest daily mean of activity, the longest duration, and the shortest circadian period length were observed on the day of estrus in both entrained and free-running animals. The day of estrus was characterized by a constant high level of activity throughout the activity phase, while the days following ovulation showed a bi- or trimodal activity pattern. Power spectrum analysis revealed significant ultradian components for the days of metestrus and diestrus, but only circadian components for the days of proestrus and estrus. These results were interpreted as indicating that endogenous changes in circulating hormone levels can induce changes in the ultradian and circadian patterns of wheel-running activity in LEW/Ztm rats.     

Drosophila ebony mutants have altered circadian activity rhythms but normal eclosion rhythms

Drosophila ebony mutants exhibit a syndrome of morphological and behavioral phenotypes that include an abnormally dark body color and defects in visual and courtship responses. We now show that mutants carrying any one of five ebony alleles display complex and variable locomotor activity rhythms. Although in the most extreme cases activity is essentially aperiodic, many individuals express short- and/or long-period activity components. Three different ebony mutants (e, e1, and e11) express free-running rhythmicity in a temperature-dependent manner; activity rhythms are robust at 28 degrees C, but weak or absent at 20 degrees C. Even while maintained in a light-dark (LD) cycle, ebony homozygotes characteristically display extremely disorganized patterns of activity; some individuals entrain with an apparently abnormal phase and/or express multiple rhythmic components. Interestingly, the visual system mutation norpA partially suppresses effects of the e1 allele, which suggests that aberrant visual system inputs might contribute to the rhythm deficits of ebony mutants. In contrast to their effects on the locomotor activity rhythm, ebony mutations have no apparent impact on the circadian rhythm of adult eclosion, and thus exert rhythm-specific effects on circadian periodicity.     

Further experiments on the relationship between the period of circadian rhythms and locomotor activity levels in hamsters.

A number of experiments in the past have demonstrated that rats and mice have shorter free-running circadian rhythms when they have access to a running wheel in their cage. Moreover, within groups of rats and hamsters, individuals making most use of their running wheels tend to have shorter circadian rhythms. However, these effects are not always evident. This article analyzes the results of four additional experiments on hamsters, some showing correlations between high activity and fast rhythms, and others not. It is suggested that failure to find this relationship occurs when there is an insufficient range of activity levels within a group. When present, correlations between locomotor activity and periodicity reflect causal links because shorter rhythms can be produced by providing a type of running wheel on which hamsters run more. The effects of possible changes in activity on circadian period should be considered when interpreting experiments on physiological manipulations of the circadian period.     

Effects of aging on food-entrained circadian rhythms in the rat

Twenty-four hour schedules of restricted food availability entrain a component of the circadian activity rhythm in rats via a food-entrainable pacemaker separate from the light-entrainable pacemaker. The effect of aging on food-entrained circadian rhythms was examined in 6 rats maintained on a restricted diurnal feeding schedule from age 3–21 months and again from 24–25 months. Food-entrainment, measured as behavioral anticipation of a 1-hr daily mealtime during the middle of the light period and persistence of this anticipation rhythm during food deprivation, was apparent in the aged rats when recorded in wheel-running cages from 20–21 months of age. Despite the long duration of restricted diurnal food access, the aged rats, like young rats, rapidly reverted to nocturnal activity when transferred to ad lib feeding. When restricted diurnal feeding was reinstated at 24 months age, these rats, now recorded in food-bin monitoring cages, required more time for a food anticipation pattern to emerge and showed a lower amplitude food anticipation rhythm compared to a group of young adult rats. These age-related changes are similar to those that characterize photically entrained circadian rhythms and suggest that both components of the rat's multioscillatory circadian timekeeping system deteriorate in parallel over the life span.     

Role of the optic lobes in the regulation of the locomotor activity rhythm of Drosophila melanogaster: behavioral analysis of neural mutants

The locomotor activity patterns of the Drosophila melanogaster brain mutants optomotor blind (omb), lobula plateless (lop), minibrain (mnb), small optic lobes (sol), sine oculis (so), and the double mutants mnb;so and sol;so, all of which show reductions in the optic lobes, were investigated and compared with those of the wild-type. In none of the mutants was the number of arrhythmic flies significantly higher than in the wild-type, indicating that the optic lobes are not the sole site of a pacemaker controlling the locomotor activity rhythm. However, these mutations greatly influence the stability of the circadian system, in that the number of flies simultaneously showing two or more circadian components increased as the optic lobe defects became more severe. In flies with the strongest reduction of the optic lobes, two free-running circadian components were found almost exclusively. This suggests a two-oscillator control of the locomotor activity. Eyeless mutants also expressing a neural mutation were entrained by light:dark (LD) cycles, but their activity pattern in LD was changed compared to the wild-type and the eyeless mutant so.     

Circadian rhythms in food intake and activity in domestic cats

Daily patterns of food intake and activity were determined for normal cats and cats with pontile lesions. Food intake in the dark and in the light of LD (light/dark) cycles were determined separately by weighing the food, and a "percentage nocturnal" score was calculated. The measure of activity was infrared photobeam interruptions, with the photobeam placed in front of the cages, over the food bowl. No differences between normal cats and cats with pontile lesions were detected for any of the measures. Food intake of cats was influenced by simulated starlight and moonlight conditions and by the presence of humans. Cats in isolation from humans and human noises exhibited random patterns of activity in constant light and free-running circadian rhythms in constant dark. Idiosyncratic differences in entrainment to LD cycles were found among cats, and the relevance of this variability is noted for studies of photoperiodic phenomena in this species.     

The dorsomedial hypothalamic nucleus is critical for the expression of food-entrainable circadian rhythms

Circadian rhythms of behavior and physiology can be entrained by daily cycles of restricted food availability, but the pathways that mediate food entrainment are unknown. The dorsomedial hypothalamic nucleus (DMH) is critical for the expression of circadian rhythms and receives input from systems that monitor food availability. Here we report that restricted feeding synchronized the daily rhythm of DMH activity in rats such that c-Fos expression in the DMH was highest at scheduled mealtime. During food restriction, unlesioned rats showed a marked preprandial rise in locomotor activity, body temperature and wakefulness, and these responses were blocked by cell-specific lesions in the DMH. Furthermore, the degree of food entrainment correlated with the number of remaining DMH neurons, and lesions in cell groups surrounding the DMH did not block entrainment by food. These results establish that the neurons of the DMH have a critical role in the expression of food-entrainable circadian rhythms.     

Splitting of the locomotor activity rhythm in rats by exposure to continuous light

Female rats exposed to low intensities (0.1-1.5 lx) of continuous light (LL), displayed regular estrous cycles and free-running circadian rhythms of locomotor activity. In most rats, as the intensity of LL was increased to greater than 2.0 lx, components within the active portion (alpha) of the locomotor rhythm remained synchronized as the periodicity of the rhythm lengthened. However, in a few rats alpha split into two components; one of which free-ran with a period shorter than 24 h, while the other free-ran with a period longer than 24 h. As soon as the two components became maximally separated they spontaneously rejoined. In most rats, estrous cycles ceased shortly after the intensity of LL was increased to greater than 2.0 lx even though the locomotor activity rhythm retained its unsplit free-running nature. These observations suggest that the multiple oscillators that control the rhythms of locomotor activity and the estrous cycle are normally coupled to one another. In certain intensities of LL, these oscillators uncouple and free-run with different periodicities, a condition which causes estrous cycles to cease and sometimes produces a split locomotor activity rhythm.     

Effects of restricted feeding cycle on the locomotor activity rhythm in the mouse Mus booduga

The effect of restricted feeding (RF) cycles on the circadian locomotor activity rhythm was studied in the nocturnal field mouse Mus booduga. Mice were presented with a 2-h meal schedule every 24 h in continuous darkness (DD), in continuous light (LL), and in a light-dark (LD) cycle. Additionally, in DD, two groups of mice were subjected to RF cycles of periodicities 22 (T22) and 26 h (T26), respectively, in order to assess the limits of entrainment. The T22 and T26 RF cycles failed to produce any entrainment of the locomotor activity rhythm, whereas some of the animals that had a free-running period (tau) close to 24 h showed stable entrainment or "relative coordination" to daily (T24) RF cycle. In LD, the locomotor activity rhythm phase advanced under the influence of the daily RF cycle when the food presentation preceded the light to dark (L to D) transition by 5-6 h. However, when the timing of food presented in the RF cycle coincided with the L to D transition, locomotor activity rhythm dissociated into two components. Some of the mice whose locomotor activity rhythm disappeared in LL showed prominent meal-AA. These results suggest that RF modifies the expression of the light-entrainable pacemaker (LEP) directly and also that in the absence of the expression of the LEP, RF can induce meal-AA.     

The role of period and phase in interactions between feeding- and light-entrainable circadian rhythms

Sixteen blind male rats were maintained on ad lib food and water for 115 days to obtain stable free-running rhythms. Fifteen rats were then exposed to restricted feeding (RF, 4 hr/cycle) for 52 days and the period of food access (T) differed from the period of the free-running rhythm (tau) by 0.05 to 0.30 hr. Among 15 animals exposed to RF, deceleration of the free-running rhythm was observed in 11 rats, small accelerations occurred in 2 rats, and tau remained unchanged in 2 rats exposed to RF and one ad lib rat. The free-running rhythm assumed the period of RF in 3 rats where T-tau was less than 0.1 hr and the change in tau persisted for 42 days after RF. However, other rats failed to synchronize their free-running rhythm despite small period differences. Although these results show that the two underlying circadian pacemaking systems are not functionally independent, they appear to be only weakly coupled.     

Effect of reproductive state on circadian periodicity in the rat

The circadian activity rhythms of adult female rats maintained under a light-dark cycle of 14 hr light, 10 hr dark (LD 14:10) or constant dim illumination (dim LL) were recorded during their 4 or 5 day estrous activity cycles and when they were pseudopregnant. In LD 14:10 both the phase angle difference (ψ), which defines the temporal relationship between the onsets of activity and darkness, and the period (τ) of locomotor activity differed significantly among the days of the 4 and 5 day estrous cycle. Activity-time (α) varied reliably only over the days of the 5 day estrous cycle. The period of the free-running activity rhythm in dim LL also differed significantly among the days of the estrous cycle. In both LD and dim LL the most positive ψ, shortest τ and longest α were observed on the day of estrus. Pseudopregnancy diminished the amplitude and altered the daily pattern of the estrous activity rhythm. We conclude that the periodicity of circadian activity systematically varies as a function of the stage of the estrous cycle and in a manner that cannot be solely explained by corresponding alterations in endogenous estrogen.