Light-entrainable Pacemaker Research Articles

Participation of the Olfactory Bulb in Circadian Organization during Early Postnatal Life in Rabbits.

Experimental evidence indicates that during pre-visual stages of development in mammals, circadian regulation is still not under the control of the light-entrainable hypothalamic pacemaker, raising the possibility that the circadian rhythmicity that occurs during postnatal development is under the control of peripheral oscillators, such as the main olfactory bulb (MOB). We evaluated the outcome of olfactory bulbectomy on the temporal pattern of core body temperature and gross locomotor activity in newborn rabbits. From postnatal day 1 (P1), pups were randomly assigned to one of the following conditions: intact pups (INT), intact pups fed by enteral gavage (INT+ENT), sham operated pups (SHAM), pups with unilateral lesions of the olfactory bulb (OBx-UNI), and pups with bilateral lesions of the olfactory bulb (OBx-BI). At the beginning of the experiment, from P1-8, the animals in all groups were fed at 11:00, from P9-13 the feeding schedule was delayed 6 h (17:00), and finally, from P14-15 the animals were subjected to fasting conditions. The rabbit pups of the INT, INT+ENT, SHAM and OBx-UNI groups exhibited a clear circadian rhythmicity in body temperature and locomotor activity, with a conspicuous anticipatory rise hours prior to the nursing or feeding schedule, which persisted even during fasting conditions. In addition, phase delays in the nursing or feeding schedule induced a clear phase shift in both parameters. In contrast, the OBx-BI group exhibited atypical rhythmicity in both parameters under entrained conditions that altered the anticipatory component, as well as deficient phase control of both rhythms. The present results demonstrate that the expression of circadian rhythmicity at behavioral and physiological levels during early stages of rabbit development largely depends on the integrity of the main olfactory bulb.

Neural activity in the suprachiasmatic circadian clock of nocturnal mice anticipating a daytime meal

Circadian rhythms in mammals are regulated by a system of circadian oscillators that includes a light-entrainable pacemaker in the suprachiasmatic nucleus (SCN) and food-entrainable oscillators (FEOs) elsewhere in the brain and body. In nocturnal rodents, the SCN promotes sleep in the day and wake at night, while FEOs promote an active state in anticipation of a predictable daily meal. For nocturnal animals to anticipate a daytime meal, wake-promoting signals from FEOs must compete with sleep-promoting signals from the SCN pacemaker. One hypothesis is that FEOs impose a daily rhythm of inhibition on SCN output that is timed to permit the expression of activity prior to a daytime meal. This hypothesis predicts that SCN activity should decrease prior to the onset of anticipatory activity and remain suppressed through the scheduled mealtime. To assess the hypothesis, neural activity in the SCN of mice anticipating a 4–5-h daily meal in the light period was measured using FOS immunohistochemistry and in vivo multiple unit electrophysiology. SCN FOS, quantified by optical density, was significantly reduced at the expected mealtime in food-anticipating mice with access to a running disk, compared to ad libitum-fed and acutely fasted controls. Group differences were not significant when FOS was quantified by other methods, or in mice without running disks. SCN electrical activity was markedly decreased during locomotion in some mice but increased in others. Changes in either direction were concurrent with locomotion, were not specific to food anticipation, and were not sustained during longer pauses. Reduced FOS indicates a net suppression of SCN activity that may depend on the intensity or duration of locomotion. The timing of changes in SCN activity relative to locomotion suggests that any effect of FEOs on SCN output is mediated indirectly, by feedback from neural or systemic correlates of locomotion.

The complex relationship between the light‐entrainable and methamphetamine‐sensitive circadian oscillators: evidence from behavioral studies of Period‐mutant mice

The methamphetamine-sensitive circadian oscillator (MASCO) is an enigmatic circadian clock whose output is observed during continuous consumption of low-dose methamphetamine. The MASCO rhythm persists when the light-entrainable pacemaker in the suprachiasmatic nucleus (SCN) is lesioned, but the anatomical location of MASCO is unknown. We recently found that the period of the MASCO rhythm is unusually short (21h) in mice with disruption of all three paralogs of the canonical clock gene, Period. In this study, we investigated the contribution of each Period paralog to timekeeping in MASCO. We measured wheel-running activity rhythms in intact and SCN-lesioned Per1-, 2- and 3-mutant mice administered methamphetamine, and found that none of the mice displayed a short (21-h) period, demonstrating that no single Period gene is responsible for the short-period MASCO rhythm of Per1(-/-) /Per2(-/-) /Per3(-/-) mice. We also found that the periods of activity rhythms in constant darkness were lengthened by methamphetamine treatment in intact wild-type, Per1(-/-) and Per3(-/-) mice but not Per2(-/-) mice, and Per2(-/-) mice had two distinct activity rhythms upon release to constant light. These data suggest that the SCN and MASCO are not coupled in Per2(-/-) mice. The MASCO rhythm in Per1(-/-) /Per2(-/-) mice in constant darkness alternated between a short (22-h) and a long (27-h) period. This pattern could result from two coupled oscillators that are not synchronised to each other, or from a single oscillator displaying birhythmicity. Finally, we propose a working model of the in vivo relationship between MASCO and the SCN that poses testable hypotheses for future studies.

Daytime restricted feeding modifies 24 h rhythmicity and subcellular distribution of liver glucocorticoid receptor and the urea cycle in rat liver

The timing system in mammals is formed by a set of peripheral biological clocks coordinated by a light-entrainable pacemaker located in the suprachiasmatic nucleus. Daytime restricted feeding (DRF) modifies the circadian control and uncouples the light-dependent physiological rhythmicity, food access becoming the principal external time cue. In these conditions, an alternative biological clock is expressed, the food-entrainable oscillator (FEO). Glucocorticoid hormones are an important part of the humoral mechanisms in the daily synchronisation of the metabolic response of peripheral oscillators by the timing system. A peak of circulating corticosterone has been reported before food access in DRF protocols. In the present study we explored in the liver the 24h variations of: (1) the subcellular distribution of glucocorticoid receptor (GCR), (2) the activities of the corticosterone-forming and NADPH-generating enzymes (11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) and hexose-6-phosphate dehydrogenase (H6PDH)), and, (3) parameters related with the urea cycle (circulating urea and activities of carbamoyl phosphate synthetase and ornithine transcarbamylase) elicited by DRF. The results showed that DRF promoted an increase of more than two times of the hepatic GCR, but exclusively in the cytosolic compartment, since the GCR in the nuclear fraction showed a reduction. No changes were observed in the activities of 11β-HSD-1 and H6PDH, but the rhythmicity of all of the urea cycle-related parameters was modified. It is concluded that liver glucocorticoid signalling and the urea cycle are responsive to feeding-restricted schedules and could be part of the FEO.

The Dorsomedial Hypothalamic Nucleus Is Not Necessary for the Expression of Circadian Food-Anticipatory Activity in Rats

Restricted daytime feeding generates food-anticipatory activity (FAA) by entrainment of a circadian pacemaker separate from the light-entrainable pacemaker located in the SCN. The dorsomedial hypothalamic nucleus (DMH) has been proposed as the site of food-entrainable oscillators critical for the expression of FAA, but another study found no effects of complete DMH ablation on FAA. To account for these different results, the authors examined methodological factors, including (1) cage configuration and feeding method and (2) use of social cues. Intact and DMH-ablated rats were maintained on one 4-h daily meal in the middle of the light period, using caging and feeding methods matching those of Gooley et al. (2006). Rats with partial or complete DMH ablation were less nocturnal during ad lib food access but exhibited normal FAA during restricted feeding, as quantified by FAA magnitude, ratios, latency to appearance, duration, and precision. To evaluate the use of social cues, intact rats naive to restricted-feeding schedules were food deprived for 72 h on 4 tests. Daytime activity increased during food deprivation, but the magnitude and waveform of this activity was not influenced by the presence of food-entrained rats exhibiting robust FAA in adjacent cages. Thus, hungry intact rats do not use social cues to anticipate a daily mealtime, suggesting that DMH-ablated rats do not anticipate meals by reacting to sounds from food-entrained intact rats in adjacent cabinets. These results confirm our previous finding that the DMH is not critical for normal expression of FAA in rats, and this observation is extended to food restriction methodologies used by other labs. The methodological differences that do underlie discrepant results remain unresolved, as does the location of food-entrainable oscillators, input pathways, and output pathways critical for FAA.

Persistence of a behavioral food-anticipatory circadian rhythm following dorsomedial hypothalamic ablation in rats

Circadian rhythms of behavior in rodents are regulated by a system of circadian oscillators, including a master light-entrainable pacemaker in the suprachiasmatic nucleus that mediates synchrony to the day-night cycle, and food-entrainable oscillators located elsewhere that generate rhythms of food-anticipatory activity (FAA) synchronized to daily feeding schedules. Despite progress in elucidating neural and molecular mechanisms of circadian oscillators, localization of food-entrainable oscillators driving FAA remains an enduring problem. Recent evidence suggests that the dorsomedial hypothalamic nucleus (DMH) may function as a final common output for behavioral rhythms and may be critical for the expression of FAA (Gooley JJ, Schomer A, and Saper CB. Nat Neurosci 9: 398-407, 2006). To determine whether the reported loss of FAA by DMH lesions is specific to one behavioral measure or generalizes to other measures, rats received large radiofrequency lesions aimed at the DMH and were recorded in cages with movement sensors. Total and partial DMH ablation was associated with a significant attenuation of light-dark-entrained activity rhythms during ad libitum food access, because of a selective reduction in nocturnal activity. When food was restricted to a single 3-h daily meal in the middle of the lights-on period, all DMH and intact rats exhibited significant FAA. The rhythm of FAA persisted during a 48-h food deprivation test and reappeared during a 72-h deprivation test after ad libitum food access. The DMH is not the site of oscillators or entrainment pathways necessary for all manifestations of FAA, but may participate on the output side of this circadian function.

Timed hypocaloric food restriction alters the synthesis and expression of vasopressin and vasoactive intestinal peptide in the suprachiasmatic nucleus

In mammals, the main circadian pacemaker is located in the suprachiasmatic nucleus (SCN) and its most potent synchronizer is the daily variation of the intensity of light. However, other nonphotic cues, such as timed food restriction, can induce changes in the circadian rhythms, leading also to the appearance of a food-entrained oscillator. The present study was designed to establish if the alterations of the circadian rhythms induced by timed hypocaloric food restriction are accompanied by structural changes in the SCN. Two groups of adult rats, both maintained on 12-h light/12-h dark cycles, were used; in one group, animals had permanent free access to food, whereas in the other they were subjected to a restricted hypocaloric early morning feeding during 7 months. Using stereological techniques and in situ hybridization, we have examined the structure of the SCN and the synthesis and expression of vasopressin (AVP) and vasoactive intestinal peptide (VIP). The volume of the SCN and the total number of neurons did not vary between the two groups. However, the total number of AVP- and VIP-immunoreactive neurons and the AVP and VIP mRNA levels were significantly decreased in timed hypocaloric food-restricted animals. The results indicate that timed hypocaloric food restriction has led to changes of AVP and VIP content of the neurons. They furthermore suggest the existence of a coupling between the food-entrainable oscillator and the light-entrainable pacemaker.

Food-entrained circadian rhythms in rats are insensitive to deuterium oxide

Rats anticipate a scheduled daily meal by entrainment of a circadian pacemaker separate from the light-entrainable circadian pacemaker located in the suprachiasmatic nuclei (SCN). The site and molecular mechanisms of the food-entrainable pacemaker are unknown. The intrinsic period ( τ) of the SCN pacemaker is significantly lengthened by deuteriation. Sensitivity of food-entrained circadian rhythms to D 2O (25% in drinking water) was evaluated in intact and SCN-ablated rats entrained to daily feeding schedules. In intact rats fed ad-libitum, D 2O lengthened τ sufficiently to drive activity rhythms out of entrainment to the light–dark cycle. By contrast, food-entrained rhythms were surprisingly resistant to modulation by D 2O. The mean daily onset time of food anticipatory activity in rats with complete SCN-ablations was not affected by up to 28 days of D 2O intake. Transient delays and disruption of anticipatory activity were evident in intact and one partial SCN-ablated rat during D 2O treatment, but these are interpretable as effects of coupling and/or masking interactions between a D 2O-sensitive light-entrainable pacemaker, and a D 2O-resistant food-entrained pacemaker. Differential sensitivity to D 2O suggests diversity in the molecular mechanisms of food- and light-entrainable circadian pacemakers in mammals. D 2O may have utility as a screening test to identify putative food-entrainable pacemakers from among those central and peripheral tissues that can express circadian oscillations of clock genes independent of the SCN.

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 (τ) 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.

Metabolic influences on circadian rhythmicity in Siberian and Syrian hamsters exposed to long photoperiods.

Calorie restriction and other situations of reduced glucose availability in rodents alter the entraining effects of light on the circadian pacemaker located in the suprachiasmatic nuclei. Siberian and Syrian hamsters are photoperiodic species that are sexually active when exposed to long summer-like photoperiods, while both species show opposite changes in body mass when transferred from long to short or short to long days. Because metabolic cues may fine tune the photoperiodic responses via the suprachiasmatic nuclei, we tested whether timed calorie restriction can alter the photic synchronization of the light-entrainable pacemaker in these two hamster species exposed to long photoperiods. Siberian and Syrian hamsters were exposed to 16 h:8 h light:dark cycles and received daily hypocaloric (75% of daily food intake) or normocaloric diet (100% of daily food intake) 4 h after light onset. Four weeks later, hamsters were transferred to constant darkness and fed ad libitum. The onset of the nocturnal pattern of locomotor activity was phase advanced by 1.5 h in calorie-restricted Siberian hamsters, but not in Syrian hamsters. The lack of phase change in calorie-restricted Syrian hamsters was also observed in individuals exposed to 14 h:10 h dim light:dark cycles and fed with lower hypocaloric food (i.e. 60% of daily food intake) 2 h after light onset. Moreover, in hamsters housed in constant darkness and fed ad lib., light-induced phase shifts of the locomotor activity in Siberian hamsters, but not in Syrian hamsters were significantly reduced when glucose utilization was blocked by pretreatment with 500 mg/kg i.p. 2-deoxy-D-glucose. Taken together, these results show that the photic synchronization of the light-entrainable pacemaker can be modulated by metabolic cues in Siberian hamsters, but not in Syrian hamsters maintained on long days.

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.

Food-Entrained Feeding and Locomotor Circadian Rhythms in Rats Under Different Lighting Conditions

It has been suggested that two endogenous timekeeping systems, a light-entrainable pacemaker (LEP) and a food-entrainable pacemaker (FEP), control circadian rhythms. To understand the function and interaction between these two mechanisms better, we studied two behavioral circadian rhythmicities, feeding and locomotor activity, in rats exposed to two conflicting zeitgebers, food restriction and light-dark cycles. For this, the food approaches and wheel-running activity of rats kept under light-dark (LD) 12:12, constant darkness (DD), or constant light (LL) conditions and subjected to different scheduled feeding patterns were continuously recorded. To facilitate comparison of the results obtained under the different lighting conditions, the period of the feeding cycles was set in all three cases about Ih less than the light-entrained or free-running circadian rhythms. The results showed that, depending on the lighting conditions, some components of the feeding and wheel-running circadian rhythms could be entrained by food pulses, while others retained their free-running or light-entrained state. Under LD, food pulses had little influence on the light-entrained feeding and loco-motor rhythms. Under DD, relative coordination between free-running and food-associated rhythms may appear. In both cases, the feeding activity associated with the food pulses could be divided into a prominent phase-dependent peak of activity within the period of food availability and another afterward. Wheel-running activity mainly followed the food pulses. Under LL conditions, the food-entrained activity consisted mainly of feeding and wheel-running anticipatory activity. The results provide new evidence that lighting conditions influence the establishment and persistence of food-entrained circadian rhythms in rats. The existence of two coupled pacemakers, LEP and FEP, or a multioscillatory LEP may both explain our experimental results.

Entrainment in calorie-restricted mice: conflicting zeitgebers and free-running conditions.

Phase-shifting effects of timed calorie restriction were investigated in mice during exposure to a 12:12-h light-dark cycle. Food-anticipatory activity (FAA), the output of a food-entrainable pacemaker, was expressed before the time of feeding whether mice received daily hypocaloric food (3.3 g of chow/day) or normocaloric food (5 g of chow/day) at zeitgeber time (ZT) 2 (ZT12 = lights off). Subsequently, mice were placed in constant darkness and fed ad libitum. The onset of the nocturnal period of locomotor activity was phase advanced by 1 h in calorie-restricted mice compared with normocalorie-fed controls. The phase advance still occurred when FAA was prevented by restraining calorie-restricted mice. Giving hypocaloric food at ZT2, ZT10, ZT14, or ZT22 phase advanced the nocturnal pattern of activity by 1, 3, 1, and 1 h, respectively. After transfer to constant darkness, FAA free ran in parallel with the normal nocturnal period of locomotor activity. A light pulse during the early subjective night phase delayed both components. These results indicate that 1) timed calorie restriction under a light-dark cycle can phase advance the light-entrainable pacemaker with a phase-dependent magnitude, 2) FAA feedback is not crucial for the observed phase advance, and 3) the light-entrainable pacemaker may control the period of the food-entrainable pacemaker in mice fed ad libitum.

Discrimination of circadian phase in intact and suprachiasmatic nuclei-ablated rats

This study examined whether the circadian system of rats can serve as a consulted clock for discriminating time of day. Food restricted rats housed in activity wheels were trained to lever press for food in a two-lever T-maze in which the left arm was correct in a morning feeding session, and the right arm in an afternoon session (7 h interval). All six rats learned the task (discrimination ratios > chance on 85–95% of sessions) and exhibited anticipatory wheel running prior to most sessions. Performance was not disrupted by inverting the LD cycle or by omitting 1–3 sessions, indicating that learning was not dependent on light-dark cues, alternation strategies, or physiological states associated with intermeal interval. Five of six additional rats with ablations of the suprachiasmatic nucleus light-entrainable pacemaker acquired the discrimination, indicating that time-of-day cues can be provided by another circadian pacemaker (likely food-entrainable). The results provide the first clear evidence that the circadian system in a mammal can function as a consulted clock that provides discriminative time cues for cognitive processes subserving behavioral plasticity.

Entrainment of Aged, Dysrhythmic Rats to a Restricted Feeding Schedule

Aged rats often display abnormal circadian activity rhythms; the rhythm amplitude is low and entrainment to light-dark cycles is irregular. The activity rhythm of young rats can be entrained by both light and nonphotic cues, specifically food availability. In young rats, entrainment to restricted feeding cycles does not depend on intact suprachiasmatic nuclei, the presumed anatomical location of the light-entrainable oscillator. In this study, aged rats that displayed disrupted entrainment to light were assessed for their ability to entrain to restricted feeding schedules. Aged rats, young controls, and young suprachiasmatic nuclei-lesioned (SCN) rats were placed on a food restriction schedule (FR) for 14 days. Food was available for 2 h during the light phase of a 12-h light-dark cycle. Despite the absence of entrainment to light/dark cycles, both SCN-lesioned and aged groups showed entrainment to FR, with clear bouts of anticipatory activity during a period of complete food deprivation following 2 weeks of FR. The results suggest that the dysrhythmia of aged rats is a result of natural deterioration of a central circadian light-entrainable pacemaker, but that a secondary oscillator entrainable to food cycles is spared.

Daily restricted feeding effects on the circadian activity rhythms of the stripe-faced dunnart, Sminthopsis macroura.

The effect of daily restricted feeding (RF) on the circadian wheel-running activity rhythms of the stripe-faced dunnart (Sminthopsis macroura) was examined. Dunnarts were presented with a 2-h meal in the middle of the light period of a 14:10 light:dark (LD) cycle and during constant dim light (LL). No meal-anticipatory activity (AA) was observed in any of the dunnarts during the experiment. This contrasts with previous work where AA has been reported in dunnarts subjected to RF. In LL, RF acted as a weak zeitgeber for the circadian activity rhythms of the dunnart. Evidence supporting this observation was the fact that 4/8 dunnarts' activity rhythms were entrained by RF, 2 showed relative coordination, and 1 exhibited bouncing phenomenon. In other species of marsupials and in rats, it has been proposed that RF entrains a food-entrainable pacemaker, which, in turn, entrains, via coupling, the suprachiasmatic-based, light-entrainable pacemaker. The findings of the present study differ from those reported previously in that no observable AA was entrained but the light-entrainable pacemaker was entrained by RF. In the dunnart, it remains to be determined whether RF directly entrains the light-entrainable pacemaker or whether RF entrains a food-entrainable pacemaker and in turn, via coupling, the light-entrainable pacemaker.

Different populations of cells in the suprachiasmatic nuclei express c- fos in association with light-induced phase delays and advances of the free-running activity rhythm in hamsters

Circadian rhythmicity is controlled by a light-entrainable pacemaker located in the suprachiasmatic nuclei (SCN) of the mammalian hypothalamus. Brief light exposure during the subjective night causes phase shifts of the free-running activity rhythm and expression of c- fos-related proteins (Fos) among a population of cells in the hamster SCN. Light exposure (30 lux for 15 min) during the early subjective night (CT13) causes phase delays (−60 ± 12 min), while exposure at mid-subective night (CT18) causes phase advances (114 ± 48 min) of t free-running activity rhythm. Light exposure at mid-subjective day (CT6) does not cause phase alterations of the rhythm. Similarity, only light exposure at CT13 or CT18 induces Fos expression in the SCN. The distributi on of Fos-immunoreactive cells in the SCN is more widespread in animals stimulated with light at CT18. In addition, a group of cells located dorsal and anterior to the SCN express Fos only after stimulation at CT18. The data are consistent with the hypothesis that Fos expression represents an event in the signal transduction pathway leading to light-induced alterations in circadian pacemaker function. Furthermore, the data raise the possibility that different populations of cells in the suprachiasmatic hypothalamus may participate in light-induced phase advances and delays of the circadian pacemaker.

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.

Daily hoarding opportunity entrains the pacemaker for hamster activity rhythms.

The effects on activity rhythms of a daily 30 min opportunity to leave the home cage and hoard seeds from an open field were assessed in Syrian hamsters housed in continuous dim illumination. Six of ten hamsters responded with clear entrainment of their activity rhythms to the hoarding opportunity, as demonstrated by responses to phase shifts and by the onset phase of subsequent freerunning rhythms. No entrainable component separate from the freerunning rhythm was ever observed. Two hamsters showed phase shifts in response to the hoarding opportunity, but they did not meet the criteria for stable entrainment, and two did not respond with noticeable changes in rhythmicity. Ablations of the suprachiasmatic nuclei (SCN) were attempted in three hamsters that had entrained stably to the hoarding time. The effects of partial lesions in two animals indicated that the entrained rhythm was controlled by the light-entrainable pacemaker represented by the SCN. The one animal with an apparently complete lesion, however, developed a clear, but irregular, increase in activity in anticipation of the daily hoarding time. SCN ablation apparently unmasked an oscillator system separate from the SCN and susceptible to entrainment by a nonphotic cue. The oscillator mechanism affected by daily hoarding opportunities in hamsters appears to be tightly coupled to the SCN pacemaker, in contrast to the system in rats that is synchronized by daily feeding schedules.