Circadian Rhythm Of Locomotor Activity Research Articles

Sex-Related Variation in Circadian Rhythms in the Bumble Bee Bombus terrestris.

Mating success depends on many factors, but first of all, a male and a female need to meet at the same place and time. The circadian clock is an endogenous system regulating activity and sex-related behaviors in animals. We studied bumble bees (Bombus terrestris) in which the influence of circadian rhythms on sexual behavior has been little explored. We characterized circadian rhythms in adult emergence and locomotor activity under different illumination regimes for males and gynes (unmated queens). We developed a method to monitor adult emergence from the pupal cocoon and found no circadian rhythms in this behavior for either males or gynes. These results are not consistent with the hypothesis that the circadian clock regulates emergence from the pupa in this species. Consistent with this premise, we found that both gynes and males do not show circadian rhythms in locomotor activity during the first 3 days after pupal emergence, but shortly after developed robust circadian rhythms that are readily shifted by a phase delay in illumination regime. We conclude that the bumble bees do not need strong rhythms in adult emergence and during early adult life in their protected and regulated nest environment, but do need strong activity rhythms for timing flights and mating-related behaviors. Next, we tested the hypothesis that the locomotor activity of males and gynes have a similar phase, which may improve mating success. We found that both males and gynes have strong endogenous circadian rhythms that are entrained by the illumination regime, but males show rhythms at an earlier age, their rhythms are stronger, and their phase is slightly advanced relative to that of gynes. An earlier phase may be advantageous to males competing to mate a receptive gyne. Our results are consistent with the hypothesis that sex-related variations in circadian rhythms is shaped by sexual selection.

7503 Light Composition Alters Feline Stress in a Shelter Environment

Abstract Disclosure: A.M. Yaw: None. M.E. Gardella: None. J. Jacobs: None. H.M. Hoffmann: None. Millions of cats enter animal shelters each year. Unfortunately, due to high numbers of cats entering shelters and limited physical housing space, over 50% of healthy and adoptable cats with extended shelter stays are euthanized yearly. While animal shelters are essential for keeping cats safe from unfit living conditions, they are a stressful environment. High stress in cats increases health risks and undesirable behaviors and is associated with reduced adoptions. Given the role of light in regulating hormonal stress responses and behavior, we partnered with a Midwestern animal control and shelter to evaluate how light intensity and light composition impact feline behavior and urinary cortisol levels in 123 domestic cats (Felis catus; 65 male and 58 female). The impact of three lighting conditions, white, dim, and orange (blue-depleted) light, were evaluated for the first 5-6 days following admittance into the shelter. Individually housed adults (8 months-10 years) were outfitted with PetPace Smart Collars to evaluate locomotor activity, and cat stress was evaluated daily through urine samples and a behavioral approach test. All data were analyzed by experimenters who were blind to the groups and tested via one or two-way ANOVA or repeated measures mixed-effects model with Geisser-Greenhouse correction. Urinary cortisol levels were dependent on both light quality and day in shelter, where cats under orange light had reduced cortisol on days 4-5 in the shelter compared to cats in standard lighting. Light quality also altered cat hiding behavior, such that the percentage of cats hiding was increased on dim light compared to both standard and orange light. A novel behavioral approach task found reduced cat stress on days 4-5 in standard and orange light; however, dim light increased cat stress on day 5 in shelter. All cats exhibited circadian rhythms in locomotor activity with periods ranging from 21.33-35.67h independent of light condition and day in shelter, and locomotor activity increased on days 3-4 compared to day 2 in the shelter, with no effect of light condition. There were no sex differences in in hiding, PetPace activity, or cat stress scores under any light condition; however, females displayed increased urinary cortisol levels compared to males in standard, but not dim or orange, light. This shows for the first time that room light manipulation can help shelters enact easy and inexpensive changes that make the adjustment period shorter and less stressful for incoming cats which will improve animal wellbeing. Presentation: 6/1/2024

Sweetened caffeine drinking revealed behavioral rhythm independent of the central circadian clock in male mice

Caffeine consumption is associated with the evening chronotype, and caffeine administration in mice results in prolonged period of the circadian rhythm in locomotor activity. However, as caffeine is bitter, sweetened caffeine is preferred by humans and mice; yet, its impact on the circadian clock has not been explored. In this study, mice were provided with freely available sweetened caffeine to investigate its effects on behavioral rhythms and peripheral clocks. Mice that freely consumed sweetened caffeine shifted from nocturnal to diurnal activity rhythms. In addition to the light-dark entrained behavioral rhythm component, some animals exhibited free-running period longer than 24-h. Intraperitoneal administration of caffeine at the beginning of the light phase also acutely induced diurnal behavior. The behavioral rhythms with long period (26–30 h) due to sweetened caffeine were observed even in mice housed under constant light or with a lesioned central circadian clock located in the suprachiasmatic nucleus of the hypothalamus; however, the rhythmicity was unstable. PER2::LUCIFERASE rhythms in peripheral tissues, such as the kidney, as measured via in vivo whole-body imaging during caffeine consumption, showed reduced amplitude and desynchronized phases among individuals. These results indicate that consumption of sweetened caffeine induces diurnal and long-period behavioral rhythms irrespective of the central clock, causing desynchronization of the clock in the body.

Divergent patterns of locomotor activity in cave isopods (Oniscidea: Styloniscidae) in Neotropics

ABSTRACT In cave environments, stable conditions devoid of light-dark cycles and temperature fluctuations sustain circadian clock mechanisms across various species. However, species adapted to these conditions may exhibit disruption of circadian rhythm in locomotor activity. This study examines potential rhythm loss due to convergent evolution in five semi-aquatic troglobitic isopod species (Crustacea: Styloniscidae), focusing on its impact on locomotor activity. The hypothesis posits that these species display aperiodic locomotor activity patterns. Isopods were subjected to three treatments: constant red light (DD), constant light (LL), and light-dark cycles (LD 12:12), totaling 1656 h. Circadian rhythm analysis employed the Sokolove and Bushell periodogram chi-square test, Hurst coefficient calculation, intermediate stability (IS), and activity differences for each species. Predominantly, all species exhibited an infradian rhythm under DD and LL. There was synchronization of the locomotor rhythm in LD, likely as a result of masking. Three species displayed diurnal activity, while two exhibited nocturnal activity. The Hurst coefficient indicated rhythmic persistence, with LD showing higher variability. LD conditions demonstrated higher IS values, suggesting synchronized rhythms across species. Significant individual variations were observed within species across the three conditions. Contrary to the hypothesis, all species exhibited synchronization under light-dark conditions. Analyzing circadian activity provides insights into organism adaptation to non-cyclical environments, emphasizing the importance of exploring underlying mechanisms.

A deleterious variant of INTS1 leads to disrupted sleep-wake cycles.

Sleep disturbances are common among children with neurodevelopmental disorders. Here, we report a syndrome characterized by prenatal microcephaly, intellectual disability and severe disruption of sleep-wake cycles in a consanguineous family. Exome sequencing revealed homozygous variants (c.5224G>A and c.6506G>T) leading to the missense mutations E1742K and G2169V in integrator complex subunit 1 (INTS1), the core subunit of the Integrator complex. Conservation and structural analyses suggest that G2169V has a minor impact on the structure and function of the complex, while E1742K significantly alters a negatively charged conserved patch on the surface of the protein. The severe sleep-wake cycles disruption in human carriers highlights a new aspect of Integrator complex impairment. To further study INTS1 pathogenicity, we generated Ints1-deficient zebrafish lines. Mutant zebrafish larvae displayed abnormal circadian rhythms of locomotor activity and sleep, as is the case with the affected humans. Furthermore, Ints1-deficent larvae exhibited elevated levels of dopamine β-hydroxylase (dbh) mRNA in the locus coeruleus, a wakefulness-inducing brainstem center. Altogether, these findings suggest a significant, likely indirect, effect of INTS1 and the Integrator complex on maintaining circadian rhythms of locomotor activity and sleep homeostasis across vertebrates.

Circadian Rhythms of Body Temperature and Locomotor Activity in Spontaneously Hypertensive Rats under Frequent Changes in Light Conditions.

Changes in lighting accompany modern urbanization trends and can lead to various pathologies based on circadian disturbances. In this study, we assessed the changes in the circadian rhythm of core body temperature (Tcore) and locomotor activity of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) following exposure to different lighting conditions: extended light phase of the day (16 h-8 h, 20 h-4 h, 24 h-0 h), light pollution, monochromatic light, and bright light therapy. The telemetry data was collected after experimental lighting conditions during periods with standard lighting (12 h of light and 12 h of darkness) and was processed using linear and cosinor analysis. The daily rhythms of rats' parameters persisted in accordance with the standard lighting regime. Tcore changes were observed in both groups compared to the initial period: in WKY, a decrease in Tcore during the darkness and an increase during the light; in SHR, the opposite trend, with Tcore increased during the darkness and decreased during the light phase of the day. A relationship between Tcore and activity was observed with weak correlation. WKY exhibited more pronounced signs of adaptive variation and desynchronization compared to SHR, which could be associated with a wider range of functional capabilities of the organism without cardiovascular pathology.

Contribution of the eye and of opn4xa function to circadian photoentrainment in the diurnal zebrafish.

The eye is instrumental for controlling circadian rhythms in mice and human. Here, we address the conservation of this function in the zebrafish, a diurnal vertebrate. Using lakritz (lak) mutant larvae, which lack retinal ganglion cells (RGCs), we show that while a functional eye contributes to masking, it is largely dispensable for the establishment of circadian rhythms of locomotor activity. Furthermore, the eye is dispensable for the induction of a phase delay following a pulse of white light at CT 16 but contributes to the induction of a phase advance upon a pulse of white light at CT21. Melanopsin photopigments are important mediators of photoentrainment, as shown in nocturnal mammals. One of the zebrafish melanopsin genes, opn4xa, is expressed in RGCs but also in photosensitive projection neurons in the pineal gland. Pineal opn4xa+ projection neurons function in a LIGHT ON manner in contrast to other projection neurons which function in a LIGHT OFF mode. We generated an opn4xa mutant in which the pineal LIGHT ON response is impaired. This mutation has no effect on masking and circadian rhythms of locomotor activity, or for the induction of phase shifts, but slightly modifies period length when larvae are subjected to constant light. Finally, analysis of opn4xa;lak double mutant larvae did not reveal redundancy between the function of the eye and opn4xa in the pineal for the control of phase shifts after light pulses. Our results support the idea that the eye is not the sole mediator of light influences on circadian rhythms of locomotor activity and highlight differences in the circadian system and photoentrainment of behaviour between different animal models.

Role of melanocortin system in the locomotor activity rhythms and melatonin secretion as revealed by agouti-signalling protein (asip1) overexpression in zebrafish.

Temporal signals such as light and temperature cycles profoundly modulate animal physiology and behaviour. Via endogenous timing mechanisms which are regulated by these signals, organisms can anticipate cyclic environmental changes and thereby enhance their fitness. The pineal gland in fish, through the secretion of melatonin, appears to play a critical role in the circadian system, most likely acting as an element of the circadian clock system. An important output of this circadian clock is the locomotor activity circadian rhythm which is adapted to the photoperiod and thus determines whether animals are diurnal or nocturnal. By using a genetically modified zebrafish strain known as Tg (Xla.Eef1a1:Cau.asip1)iim04, which expresses a higher level of the agouti signalling protein 1 (Asip1), an endogenous antagonist of the melanocortin system, we observed a complete disruption of locomotor activity patterns, which correlates with the ablation of the melatonin daily rhythm. Consistent with this, in vitro experiments also demonstrated that Asip1 inhibits melatonin secretion from the zebrafish pineal gland, most likely through the melanocortin receptors expressed in this gland. Asip1 overexpression also disrupted the expression of core clock genes, including per1a and clock1a, thus blunting circadian oscillation. Collectively, these results implicate the melanocortin system as playing an important role in modulating pineal physiology and, therefore, circadian organisation in zebrafish.

Spatial distribution and circadian locomotor activity of invasive armored catfish (Loricariidae) in the freshwater and brackish water.

Invasive suckermouth armored catfish Pterygoplichthys spp. successfully spread during one decade into many river systems of Vietnam. Wide and rapid invasion of armored catfish might be associated with using brackish water in estuaries to spread from one river system to another. The first goal of our study was to assess the horizontal and vertical distribution of invasive fish in freshwater (Da Rang River) and in brackish water (Da Rang River estuary) associated with circadian rhythm. In the both sampling locations, fish were mainly caught at nighttime at the bottom and near the surface using the net traps and vertical nets. In estuary, fish were caught in the net traps with distance 2.0-7.5 m from the right or left banks where water was predominantly fresh. In freshwater of the Da Rang River, fish were often caught near the left bank with gravel and stone substrate. The second goal of our study was to experimentally evaluate the circadian (12 hours of the night and 12 hours of the day) rhythm of locomotor activity (LA) of fish. Fish from different freshwater locations (Am Chua canal and Da Rang River) had a similar diurnal dynamic of LA with mostly movements (77-83% of total diurnal LA) at nighttime (18:00-6:00, GMT+7) at the end of the wet season. Armored catfish from the brackish water location (Da Rang River estuary) also were mostly active (76% of total diurnal LA) overnight. However, fish from freshwater and brackish water had difference in the timing of behavioral activity. Fish LA from estuary was significantly lower than LA of fish from freshwater locations during 18:00 to 21:00 before low tide. The results of our field and experimental studies established that armored catfish in estuary moved in horizontal and vertical planes predominantly at nighttime. Tide level regulates locomotor activity of invasive fish and could influence on the possibility of their spreading through the estuary.

Circadian Rhythms of Locomotor Activity Mediated by Cryptochrome 2 and Period 1 Genes in the Termites Reticulitermes chinensis and Odontotermes formosanus.

Locomotor activity rhythms are crucial for foraging, mating and predator avoidance in insects. Although the circadian rhythms of activity have been studied in several termite species, the molecular mechanisms of circadian rhythms in termites are still unclear. In this study, we found that two termite species, R. chinensis and O. formosanus, exhibited clear circadian rhythms of locomotor activity in constant darkness along with rhythmically expressed core clock genes, Cry2 and Per1. The knockdown of Cry2 or Per1 expression in the two termite species disrupted the circadian rhythms of locomotor activity and markedly reduced locomotor activity in constant darkness, which demonstrates that Cry2 and Per1 can mediate the circadian rhythms of locomotor activity in termites in constant darkness. We suggest that locomotor activity in subterranean termites is controlled by the circadian clock.

The presence/absence of conspecifics modulates the circadian locomotor activity and body mass in spotted munia (Lonchura punctulata)

ABSTRACT Biological clocks regulate the behavior and physiology of animals by tracking the local time using diverse time cues. Social cues are relevant in studying the behavior of gregarious animals, but these cues have not been widely studied in birds. Temporal information for circadian timekeeping is socially communicated through visual, physical, olfactory, and auditory means. We examined the efficacy of pulsatile social interactions on locomotor activity and its associated characteristics such as distribution profile of rest and activity, total counts, activity duration, phase shift in activity onset, and circadian periodicity in spotted munia. Besides, we analyzed the effect of such social interactions on their body mass. Spotted munia exhibited phase shift in the onset of activity when subjected to social isolation, but these cues could not affect their circadian periodicity. In Pair as well as in Group, social isolation led to increased activity and activity duration, and decreased body mass in guests relative to the host bird. Our results suggest that the circadian rhythm of locomotor activity in spotted munia is quite sensitive to socialization and isolation, and isolation is detrimental for the birds. Consistent with these observations, the decline in body mass revealed the physiological consequences of social isolation on spotted munia.

Transcriptional regulation of the mouse EphA4, Ephrin-B2 and Ephrin-A3 genes by the circadian clock machinery

ABSTRACT Circadian rhythms originate from molecular feedback loops. In mammals, the transcription factors CLOCK and BMAL1 act on regulatory elements (i.e. E-boxes) to shape biological functions in a rhythmic manner. The EPHA4 receptor and its ligands Ephrins (EFN) are cell adhesion molecules regulating neurotransmission and neuronal morphology. Previous studies showed the presence of E-boxes in the genes of EphA4 and specific Ephrins, and that EphA4 knockout mice have an altered circadian rhythm of locomotor activity. We thus hypothesized that the core clock machinery regulates the gene expression of EphA4, EfnB2 and EfnA3. CLOCK and BMAL1 (or NPAS2 and BMAL2) were found to have transcriptional activity on distal and proximal regions of EphA4, EfnB2 and EfnA3 putative promoters. A constitutively active form of glycogen synthase kinase 3β (GSK3β; a negative regulator of CLOCK and BMAL1) blocked the transcriptional induction. Mutating the E-boxes of EphA4 distal promoter sequence reduced transcriptional induction. EPHA4 and EFNB2 protein levels did not show circadian variations in the mouse suprachiasmatic nucleus or prefrontal cortex. The findings uncover that core circadian transcription factors can regulate the gene expression of elements of the Eph/Ephrin system, which might contribute to circadian rhythmicity in biological processes in the brain or peripheral tissues.

The unfixed light pattern contributes to depressive-like behaviors in male mice

Light pollution is now associated with an increased incidence of mental disorders in humans, and the unfixed light pattern (ULP) is a common light pollution that occurs in such as rotating shift work. However, how much contribution the ULP has to depression and its potential mechanism are yet unknown. Our study aimed to investigate the effect of the ULP on depressive-like behaviors in mice and to explore the links to the circadian-orexinergic system. Male C57BL/6 J mice were exposed to the ULP by subjecting them to an alternating light pattern every 6 days for 54 days. The tail suspension test (TST) and forced swimming test (FST) were conducted to assess depressive-like behaviors. The rhythm of locomotor activity and the circadian expression of cFOS in the suprachiasmatic nucleus (SCN), clock genes in the liver, and corticosterone (CORT) in serum were detected to observe changes in the circadian system. The circadian expression of orexin-A (OX-A) in the lateral hypothalamus area (LHA) and dorsal raphe nucleus (DRN) and serotonin (5-HT) in the DRN were measured to determine alterations in the orexinergic system. The results showed that mice exposed to the ULP exhibited increased immobility time in the TST and FST. The ULP significantly disrupted the circadian rhythm of locomotor activity, clock genes in the liver, and CORT in the serum. Importantly, when exposed to the ULP, cFOS expression in the SCN showed decreased amplitude. Its projection area, the LHA, had a lower mesor of OX-A expression. OX-A projection to the DRN and 5-HT expression in the DRN were reduced in mesor. Our research suggests that the ULP contributes to depressive-like behaviors in mice, which might be related to the reduced amplitude of circadian oscillation in the SCN and hypoactivity of the orexinergic system. These findings may provide novel insights into rotating shift work-related depression.

Long days restore regular estrous cyclicity in mice lacking circadian rhythms

Many female mammals have recurring cycles of ovulation and sexual behaviors that are regulated by reproductive hormones and confer reproductive success. In addition to sexual behaviors, circadian behavioral rhythms of locomotor activity also fluctuate across the estrous cycle in rodents. Moreover, there is a bidirectional relationship between circadian rhythms and estrous cyclicity since mice with disrupted circadian rhythms also have compromised estrous cycles resulting in fewer pregnancies. In the present study, we assessed whether extending day length, which alters circadian rhythms, normalizes estrous cyclicity in mice. We found that Period (Per) 1/2/3 triple knockout (KO) mice, that have disabled canonical molecular circadian clocks, have markedly disrupted estrous cycles. Surprisingly, extending the day length by only 2 h per day restored regular 4- or 5-day estrous cycles to Per1/2/3 KO mice. Longer days also induced consistent 4-day, rather than 5-day, estrous cycles in wild-type C57BL/6J mice. These data demonstrate that extending daytime light exposure could be used for enhancing reproductive success.

Circulating blood eNAMPT drives the circadian rhythms in locomotor activity and energy expenditure

Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor of critical enzymes including protein deacetylase sirtuins/SIRTs and its levels in mammalian cells rely on the nicotinamide phosphoribosyltransferase (NAMPT)-mediated salvage pathway. Intracellular NAMPT (iNAMPT) is secreted and found in the blood as extracellular NAMPT (eNAMPT). In the liver, the iNAMPT−NAD+ axis oscillates in a circadian manner and regulates the cellular clockwork. Here we show that the hypothalamic NAD+ levels show a distinct circadian fluctuation with a nocturnal rise in lean mice. This rhythm is in phase with that of plasma eNAMPT levels but not with that of hypothalamic iNAMPT levels. Chemical and genetic blockade of eNAMPT profoundly inhibit the nighttime elevations in hypothalamic NAD+ levels as well as those in locomotor activity (LMA) and energy expenditure (EE). Conversely, elevation of plasma eNAMPT by NAMPT administration increases hypothalamic NAD+ levels and stimulates LMA and EE via the hypothalamic NAD+−SIRT−FOXO1−melanocortin pathway. Notably, obese animals display a markedly blunted circadian oscillation in blood eNAMPT−hypothalamic NAD+−FOXO1 axis as well as LMA and EE. Our findings indicate that the eNAMPT regulation of hypothalamic NAD+ biosynthesis underlies circadian physiology and that this system can be significantly disrupted by obesity.

Nonphotic entrainment of central and peripheral circadian clocks in mice by scheduled voluntary exercise under constant darkness.

In mammals, the central circadian pacemaker in the suprachiasmatic nucleus (SCN) entrains to an environmental light-dark (LD) cycle and organizes the temporal order of circadian rhythms in physiology and behavior. Previously, some studies have demonstrated that scheduled exercise could entrain the free-running behavior rhythm in nocturnal rodents. However, it remains unknown whether entrainment by scheduled exercise alters the internal temporal order of the behavioral circadian rhythms or clock gene expression in the SCN, extra-SCN brain regions, and peripheral organs when mice are entrained to the scheduled exercise under constant darkness (DD). In the present study, we examined circadian rhythms in locomotor activity and clock gene Per1 expression by bioluminescence reporter (Per1-luc) in the SCN, arcuate nucleus (ARC), liver, and skeletal muscle of mice entrained to an LD cycle, mice free-running under DD, and mice entrained to daily exposure to a new cage with a running wheel (NCRW) under DD. All mice showed a steady-state entrainment of behavioral circadian rhythms to NCRW exposure under DD in parallel with shortening of the α when compared with that under DD. The temporal order of behavioral circadian rhythms and the Per1-luc rhythms in the SCN and peripheral tissues but not in the ARC were maintained in the mice entrained to the NCRW and LD cycles; in contrast, the temporal order was altered in the mice under DD. The present findings reveal that the SCN entrains to daily exercise, and daily exercise reorganizes the internal temporal order of behavioral circadian rhythms and clock gene expression in the SCN and peripheral tissues.

Disturbed circadian rhythm of locomotor activity of pullets is related to feather pecking in laying hens

Various aspects of activity, such as spontaneous activity, explorative activity, activity in open-field tests, and hyperactivity syndrome have been explored as causal factors of feather pecking in laying hens, with no clear results. In all previous studies, mean values of activity over different time intervals were used as criteria. Incidental observation of alternated oviposition time in lines selected for high (HFP) and low feather pecking (LFP), supported by a recent study which showed differentially expressed genes related to the circadian clock in the same lines, led to the hypothesis that feather pecking may be related to a disturbed diurnal activity rhythm. Hence activity recordings of a previous generation of these lines have been reanalyzed. Data sets of a total of 682 pullets of 3 subsequent hatches of HFP, LFP, and an unselected control line (CONTR) were used. Locomotor activity was recorded in pullets housed in groups of mixed lines in a deep litter pen on 7 consecutive 13-h light phases, using a radio-frequency identification antenna system. The number of approaches to the antenna system was recorded as a measure of locomotor activity and analyzed using a generalized linear mixed model including hatch, line, time of day and the interactions of hatch×time of day and line×time of day as fixed effects. Significant effects were found for time and the interaction line×time of day but not for line. All lines showed a bimodal pattern of diurnal activity. The peak activity of the HFP in the morning was lower than that of the LFP and CONTR. In the afternoon peak all lines differed with the highest mean in the LFP followed by CONTR and HFP. The present results provide support for the hypothesis that a disturbed circadian clock plays a role in the development of feather pecking.

Rest phase snacking increases energy resorption and weight gain in male mice

ObjectiveSnacking, i.e., the intake of small amounts of palatable food items, is a common behavior in modern societies, promoting overeating and obesity. Shifting food intake into the daily rest phase disrupts circadian rhythms and is also known to stimulate weight gain. We therefore hypothesized that chronic snacking in the inactive phase may promote body weight gain and that this effect is based on disruption of circadian clocks. MethodsMale mice were fed a daily chocolate snack either during their rest or their active phase and body weight development and metabolic parameters were investigated. Snacking experiments were repeated in constant darkness and in clock-deficient mutant mice to examine the role of external and internal time cues in mediating the metabolic effects of snacking. ResultsChronic snacking in the rest phase increased body weight gain and disrupted metabolic circadian rhythms in energy expenditure, body temperature, and locomotor activity. Additionally, these rest phase snacking mice assimilated more energy during the inactive phase. Body weight remained increased in rest phase snacking wildtype mice in constant darkness as well as in clock-deficient mutant mice under a regular light–dark cycle compared to mice snacking in the active phase. Weight gain effects were abolished in clock-deficient mice in constant darkness. ConclusionsOur data suggest that mistimed snacking increases energy resorption and promotes body weight gain. This effect requires a functional circadian clock at least under constant darkness conditions.

Detection of circadian rhythm disturbance of carbachol-induced beta wave dynamics in rat hippocampal slices using neural networks

Rats exhibit a circadian rhythm of locomotor activity. Recently, the relation between circadian rhythm and memory has been elucidated. Brain waves are related to memory processes and are modulated by circadian rhythm. Beta wave-like oscillations within 13–30 Hz can be induced by using carbachol, a cholinergic agonist, in rat hippocampal slices. In this study, we prepared hippocampal slices from rats maintained under light/dark (LD) or dark/dark (DD) conditions. We previously reported that carbachol-induced beta oscillations (CIBO) appeared at all times of the day, and oscillatory parameters, such as duration and inter-burst intervals, demonstrated significant diurnal changes. We also studied whether the time of day can be predicted using CIBO parameters and whether circadian disturbances can be detected with these parameters. Using CIBO parameters, a higher accuracy rate was obtained for time-of-day prediction than that when using the amount of locomotor activity during the day. The time of day was not correctly predicted when the parameters were applied under the DD condition, using the CIBO-parameter-trained neural network under LD conditions. Using the oscillatory parameters of the brain waves induced in the neuronal circuit will estimate the internal subjective time of the day and detect circadian disturbances such as DD condition. (199 words).

Cognitive changes and circadian timekeeping disturbances in aging

AbstractBackgroundCognitive changes in aging and Alzheimer’s disease (AD) are often accompanied by pronounced disturbances of circadian timekeeping, especially sleep‐wake cycle. Normal circadian timekeeping has an important impact on human health and performance by providing the temporal coordination of internal processes to insure their occurrence at the “right time” relative to each other and to the external environment. Aging of the rodent circadian system is characterized by changes comparable to those in human aging and AD. Common disturbances in the sleep‐wake rhythms of aged rodents include alterations in the light‐dark entrainment of this circadian rhythm. However, not all aged rodents show these changes, demonstrating the variability characteristic of human aging in pre‐dementia. The aging population also shows variability in onset and magnitude of cognitive impairment, but the relationship between these deficits with circadian rhythm disturbances has not yet been identified.MethodInitially, we tested young (3‐5 mon) and aged (18‐24 mon) C57Bl6 mice on wheel running activity continuously for 30‐40 days for circadian rhythm of locomotor activity. We then assessed learning and memory in the same mice using the Barnes maze task. Next, we wanted to determine if behavioral deficits occurred earlier in the lifespan (middle age) and whether changes in circadian activity occur prior to cognitive impairment.ResultAged mice were significantly impaired in all measures of activity rhythm entrainment and cognition. Interestingly, we observed a gender‐specific relationship between cognitive impairment in the Barnes maze and activity onset in aged female mice (20‐24 mon). Changes in activity rhythm entrainment were observed as early as 12‐14 months in middle aged mice. We also tested these mice for cognition (Barnes maze, novel and spatial recognition tests, 3 chamber sociability test) and motor behavior (rotarod, open field and digigait).ConclusionThis data will be the foundation of our model to further understand the relationship between circadian synchronization and age‐related cognitive impairment, and to probe possible mechanisms of action.