Circadian Activity Rhythms Research Articles

The locomotory activity patterns of the arid-dwelling desert hedgehog, Paraechinus aethiopicus, from Saudi Arabia

The animal-environment interaction is complex, and the ability to temporally organise locomotor activity provides adaptive and survival advantages. The daily and circadian rhythms of locomotor activity in the Desert hedgehog, Paraechinus aethiopicus, from the central deserts of Saudi Arabia were investigated under controlled laboratory conditions. Twelve individuals were subjected to different light cycles of approximately 3 weeks each: light/dark (12:12LD) cycle; a period of constant darkness (DD); an inverse of the LD (12:12 DL) cycle; a short day cycle (8:16LD); and a long day cycle (16:8LD). All the animals exhibited entrainment of their activity to the LD and DL lighting regimes. Locomotor activity of the Desert hedgehog occurred mostly during the dark phases of the LD, DL, long day and short day cycles. All entraining hedgehogs showed daily rhythmicity, with the periods of the rhythms very close to 24 h. Entrained hedgehogs, additionally, inversed their activity patterns when the light cycle was inversed. The Desert hedgehog, therefore, can be described as genuinely nocturnal with an endogenous rhythm of locomotor activity.

Secretin receptor-deficient mice exhibit altered circadian rhythm in wheel-running activity

In mammals, the timing of behavior and physiological activity is controlled by the suprachiasmatic nucleus (SCN) in the hypothalamus. Incidentally, secretin is a peptide hormone that promotes digestive activities and regulates water reabsorption. In recent studies, exogenous administration of secretin has been reported to induce secretion of oxytocin in the supraoptic nucleus of the hypothalamus and modulate social behavior. These results indicate that secretin is involved in the neural network that controls social behavior and plays important roles in the central nervous system. In the present study, we investigated the effects of secretin on circadian rhythms, by assessing circadian rhythms during wheel-running behavior in secretin receptor-deficient (Sctr−/−) mice. Male adult wild-type (WT) and Sctr-/- mice were housed in separate cages containing a wheel. Every minute of the wheel-running activity was monitored during the normal light-dark (LD) cycle (12:12 h) and in constant darkness (DD). Significant differences were observed in the free-running period between the WT and Sctr−/− mice. However, no significant differences were observed in the daily wheel-running revolutions between WT and Sctr−/− mice, in the LD and DD conditions. Moreover, the ratio of the daily activity phase to the rest phase (α/ρ) was significantly smaller in Sctr−/− than that in WT mice in the DD condition. Secretin receptors were expressed in the SCN cells. These findings suggest that secretin receptors are involved in the central circadian clock in the SCN and the circadian system in general.

Dietary natural cocoa ameliorates disrupted circadian rhythms in locomotor activity and sleep-wake cycles in mice with chronic sleep disorders caused by psychophysiological stress.

Cocoa contains many chemical compounds that affect the physiological functions of experimental animals and humans. The present study used a mouse model characterized by disrupted circadian rhythms of locomotor activity and sleep-wake cycles to determine whether natural cocoa improves chronic sleep disorders (CSDs) induced by psychophysiological stress. Mice were fed a high-fat, high-sucrose diet supplemented with 2.0% natural cocoa and stressed for 30 d to induce CSDs. Dietary cocoa restored the amplitude reduction of day-night activity rhythms by improving reduced nocturnal wheel-running activities during CSDs. Electroencephalography revealed that dietary cocoa significantly ameliorated CSD-induced increases in wakefulness during the first half of the inactive phase and in nonrapid eye movement sleep during the first half of the active phase. The attenuation of circadian rapid eye movement sleep rhythms and increased electroencephalography slow-wave activity (a marker of nonrapid eye movement sleep intensity) induced by CSDs improved in mice supplemented with cocoa. Dietary cocoa notably did not affect wheel-running activity rhythms or sleep-wake cycles under normal conditions. Dietary cocoa significantly increased the hypothalamic mRNA expression of Hspa1 a that encodes HSP70 and is associated with sleep regulation. Furthermore, Hspa1 a expression was not induced by CSDs in mice supplemented with cocoa. These findings suggest that dietary cocoa exerts beneficial effects on insomnia and circadian sleep disorders induced by psychophysiological stress.

Food as circadian time cue for appetitive behavior.

Feeding schedules entrain circadian clocks in multiple brain regions and most peripheral organs and tissues, thereby synchronizing daily rhythms of foraging behavior and physiology with times of day when food is most likely to be found. Entrainment of peripheral clocks to mealtime is accomplished by multiple feeding-related signals, including absorbed nutrients and metabolic hormones, acting in parallel or in series in a tissue-specific fashion. Less is known about the signals that synchronize circadian clocks in the brain with feeding time, some of which are presumed to generate the circadian rhythms of food-anticipatory activity that emerge when food is restricted to a fixed daily mealtime. In this commentary, I consider the possibility that food-anticipatory activity rhythms are driven or entrained by circulating ghrelin, ketone bodies or insulin. While evidence supports the potential of these signals to participate in the induction or amount of food-anticipatory behavior, it falls short of establishing either a necessary or sufficient role or accounting for circadian properties of anticipatory rhythms. The availability of multiple, circulating signals by which circadian oscillators in many brain regions might entrain to mealtime has supported a view that food-anticipatory rhythms of behavior are mediated by a broadly distributed system of clocks. The evidence, however, does not rule out the possibility that multiple peripheral and central food-entrained oscillators and feeding-related signals converge on circadian oscillators in a defined location which ultimately set the phase and gate the expression of anticipatory activity rhythms. A candidate location is the dorsal striatum, a core component of the neural system which mediates reward, motivation and action and which contains circadian oscillators entrainable by food and dopaminergic drugs. Systemic metabolic signals, such as ghrelin, ketones and insulin, may participate in circadian food anticipation to the extent that they modulate dopamine afferents to circadian clocks in this area.

Activity Tracker-Based Metrics as Digital Markers of Cardiometabolic Health in Working Adults: Cross-Sectional Study.

BackgroundGreater adoption of wearable devices with multiple sensors may enhance personalized health monitoring, facilitate early detection of some diseases, and further scale up population health screening. However, few studies have explored the utility of data from wearable fitness trackers in cardiovascular and metabolic disease risk prediction.ObjectiveThis study aimed to investigate the associations between a range of activity metrics derived from a wearable consumer-grade fitness tracker and major modifiable biomarkers of cardiometabolic disease in a working-age population.MethodsThis was a cross-sectional study of 83 working adults. Participants wore Fitbit Charge 2 for 21 consecutive days and went through a health assessment, including fasting blood tests. The following clinical biomarkers were collected: BMI, waist circumference, waist-to-hip ratio, blood pressure, triglycerides (TGs), high-density lipoprotein (HDL) and low-density lipoprotein cholesterol, and blood glucose. We used a range of wearable-derived metrics based on steps, heart rate (HR), and energy expenditure, including measures of stability of circadian activity rhythms, sedentary time, and time spent at various intensities of physical activity. Spearman rank correlation was used for preliminary analysis. Multiple linear regression adjusted for potential confounders was used to determine the extent to which each metric of activity was associated with continuous clinical biomarkers. In addition, pairwise multiple regression was used to investigate the significance and mutual dependence of activity metrics when two or more of them had significant association with the same outcome from the previous step of the analysis.ResultsThe participants were predominantly middle aged (mean age 44.3 years, SD 12), Chinese (62/83, 75%), and male (64/83, 77%). Blood biomarkers of cardiometabolic disease (HDL cholesterol and TGs) were significantly associated with steps-based activity metrics independent of age, gender, ethnicity, education, and shift work, whereas body composition biomarkers (BMI, waist circumference, and waist-to-hip ratio) were significantly associated with energy expenditure–based and HR-based metrics when adjusted for the same confounders. Steps-based interdaily stability of circadian activity rhythm was strongly associated with HDL (beta=5.4 per 10% change; 95% CI 1.8 to 9.0; P=.005) and TG (beta=−27.7 per 10% change; 95% CI −48.4 to −7.0; P=.01). Average daily steps were negatively associated with TG (beta=−6.8 per 1000 steps; 95% CI −13.0 to −0.6; P=.04). The difference between average HR and resting HR was significantly associated with BMI (beta=−.5; 95% CI −1.0 to −0.1; P=.01) and waist circumference (beta=−1.3; 95% CI −2.4 to −0.2; P=.03).ConclusionsWearable consumer-grade fitness trackers can provide acceptably accurate and meaningful information, which might be used in the risk prediction of cardiometabolic disease. Our results showed the beneficial effects of stable daily patterns of locomotor activity for cardiometabolic health. Study findings should be further replicated with larger population studies.

The influence of population-control methods and seasonality on the activity pattern of wild boars (Sus scrofa) in high-altitude forests

The wild boar (Sus scrofa) is a problematic invasive species which has colonized the threatened Brazilian Atlantic Forest. Our objective was to evaluate if population control and seasonality affect the circadian rhythm of wild boar activity. Wild boar activity was monitored by camera-traps for 1 year without population-control methods and 1 year with population-control methods implemented in the area. Before population control was implemented, wild boar activity was uniform across 24 h, with animals being active at any given time (cathemeral). After the population control, wild boars concentrated their activities on the daylight period. Also, wild boars were more active during the wet season, possibly influenced by the presence of seeds of Araucaria angustifolia trees. Based on these results, control measures should be conducted during the wet season and different management strategies, such as the use of rifles with telescopic sights and silencers, should be tested.

Chronically skipping breakfast impairs hippocampal memory-related gene expression and memory function accompanied by reduced wakefulness and body temperature in mice

Acute or chronic effects of consuming or skipping breakfast on cognitive performance in humans are controversial. To evaluate the effects of chronically skipping breakfast (SB) on hippocampus-dependent long-term memory formation, we examined hippocampal gene expression and applied the novel object recognition test (NORT) after two weeks of repeated fasting for six hours from lights off to mimic SB in mice. We also examined the effects of SB on circadian rhythms of locomotor activity, food intake, core body temperature (CBT) and sleep-wake cycles. Skipping breakfast slightly but significantly decreased total daily food intake without affecting body weight gain. Locomotor activity and CBT significantly decreased during the fasting period under SB. The degree of fasting-dependent CBT reduction gradually increased and then became stabilized after four days of SB. Electroencephalographic data revealed that repeated SB significantly decreased the duration of wakefulness and increased that of rapid eye movement (REM) and of non-REM (NREM) sleep during the period of SB. Furthermore, total daily amounts of wakefulness and NREM sleep were significantly decreased and increased, respectively, under SB, suggesting that SB disrupts sleep homeostasis. Skipping breakfast significantly suppressed mRNA expression of the memory-related genes, Camk2a, Fkbp5, Gadd45b, Gria1, Sirt1 and Tet1 in the hippocampus. Recognition memory assessed by NORT was impaired by SB in accordance with the gene expression profiles. These findings suggested that chronic SB causes dysregulated CBT, sleep-wake cycles and hippocampal gene expression, which results in impaired long-term memory formation.

A Homeobox Transcription Factor Scarecrow (SCRO) Negatively Regulates Pdf Neuropeptide Expression through Binding an Identified cis-Acting Element in Drosophila melanogaster.

In Drosophila, transcriptional feedback loops contribute to intracellular timekeeping mechanisms responsible for daily rhythms. Pigment-dispersing factor (PDF) is the major neuropeptide produced by latero-ventral neurons (LNvs) that function as a central pacemaker for circadian locomotor activity rhythms. PDF synchronizes other clock neurons thereby playing an essential role in the maintenance and coordination of circadian locomotor rhythms. However, the underlying molecular mechanism of the LNvs-specific Pdf expression is not well understood. Here, using Pdf promoter-bashing experiment, we identified a cis-acting Pdf regulatory element (PRE) that is sufficient for driving Pdf expression in the LNvs. We have also identified a homeobox transcription factor, scarecrow (SCRO), as a direct binding factor to PRE. Furthermore, transgenic expression of scro in the clock neurons abolished Pdf expression and circadian locomotor activity rhythms, and such repressive function requires DNA-binding homeodomain, but none of the other conserved domains. scro is predominantly expressed in the optic lobe and various clusters of cells in other areas of the central nervous system. A homozygous scro-null mutant generated by CRIPSR is lethal during embryonic and early larval development, suggesting that scro plays a vital role during early development.

Actigraphy for Assessing Light Effects on Sleep and Circadian Activity Rhythm in Alzheimer's Dementia: A Narrative Review.

Alzheimer's Disease (AD) is often accompanied by severe sleep problems and circadian rhythm disturbances which may to some extent be attributed to a dysfunction in the biological clock. The 24-h light/dark cycle is the strongest Zeitgeber for the biological clock. People with AD, however, often live in environments with inappropriate photic Zeitgebers. Timed bright light exposure may help to consolidate sleep- and circadian rest/activity rhythm problems in AD, and may be a low-risk alternative to pharmacological treatment. In the present review, experts from several research disciplines summarized the results of twenty-seven light intervention studies which used wrist actigraphy to measure sleep and circadian activity in AD patients. Taken together, the findings remain inconclusive with regard to beneficial light effects. However, the considered studies varied substantially with respect to the utilized light intervention, study design, and usage of actigraphy. The paper provides a comprehensive critical discussion of these issues. Fusing knowledge across complementary research disciplines has the potential to critically advance our understanding of the biological input of light on health and may contribute to architectural lighting designs in hospitals, as well as our homes and work environments.

Circadian Activity Rhythm in Early Relapsing-Remitting Multiple Sclerosis.

While relapsing–remitting is the most prevalent course of multiple sclerosis, the prognostic/predictive markers of the worsening of symptomatology are still debated. With reference to other diseases, the study of the circadian activity rhythm, according to the theoretical framework of the two-process model of sleep regulation and applying functional linear modeling, proved to be useful to identify a possible marker. The usefulness of the study of circadian activity rhythm in multiple sclerosis is strengthened by recent findings indicating a potential involvement of circadian factors in the multifactorial etiopathology of the disorder. The aim of the present study was to verify whether circadian activity rhythm of early relapsing–remitting multiple sclerosis patients presents specific alterations, through functional linear modeling. Thirty-five relapsing–remitting multiple sclerosis patients (24 females; mean age ± SD = 31.51 ± 7.74) and 35 healthy controls (24 females; mean age ± SD = 31.29 ± 8.02) were enrolled. They wore an actigraph around the non-dominant wrist for one week. Relapsing–remitting multiple sclerosis patients showed a peak in motor activity around 5:00 a.m., higher than that of healthy controls. The timing of the peak in motor activity in the patients could be explained according to the hyperactive hypothalamus-pituitary-adrenal axis and higher cortisol awakening response reported in these patients.

Pituitary Adenylate Cyclase-Activating Peptide (PACAP)-Glutamate Co-transmission Drives Circadian Phase-Advancing Responses to Intrinsically Photosensitive Retinal Ganglion Cell Projections by Suprachiasmatic Nucleus

Results from a variety of sources indicate a role for pituitary adenylate cyclase-activating polypeptide (PACAP) in light/glutamate-induced phase resetting of the circadian clock mediated by the retinohypothalamic tract (RHT). Attempts to block or remove PACAP’s contribution to clock-resetting have generated phenotypes that differ in their responses to light or glutamate. For example, previous studies of circadian behaviors found that period-maintenance and early-night phase delays are intact in PACAP-null mice, yet there is a consistent deficit in behavioral phase-resetting to light stimulation in the late night. Here we report rodent stimulus–response characteristics of PACAP release from the RHT, and map these to responses of the suprachiasmatic nucleus (SCN) in intact and PACAP-deficient mouse hypothalamus with regard to phase-resetting. SCN of PACAP-null mice exhibit normal circadian rhythms in neuronal activity, but are “blind” to glutamate stimulating phase-advance responses in late night, although not in early night, consistent with previously reported selective lack of late-night light behavioral responsiveness of these mice. Induction of CREB phosphorylation, a hallmark of the light/glutamate response of the SCN, also is absent in SCN-containing ex vivo slices from PACAP-deficient mouse hypothalamus. PACAP replacement to the SCN of PACAP-null mice restored wild-type phase-shifting of firing-rate patterns in response to glutamate applied to the SCN in late night. Likewise, ex vivo SCN of wild-type mice post-orbital enucleation are unresponsive to glutamate unless PACAP also is restored. Furthermore, we demonstrate that the period of efficacy of PACAP at SCN nerve terminals corresponds to waxing of PACAP mRNA expression in ipRGCs during the night, and waning during the day. These results validate the use of PACAP-deficient mice in defining the role and specificity of PACAP as a co-transmitter with glutamate in ipRGC-RHT projections to SCN in phase advancing the SCN circadian rhythm in late night.

Longitudinal association between circadian activity rhythms and risk of incident parkinson's disease in older men

Longitudinal association between circadian activity rhythms and risk of incident parkinson's disease in older men

Effect of duration, and temporal modulation, of monochromatic light on emmetropization in chicks

Previous experiments disagree on the effect of monochromatic light on emmetropization. Some species respond to wavelength defocus created by longitudinal chromatic aberration and become more myopic in monochromatic red light and more hyperopic in monochromatic blue light, while other species do not. Using the chicken model, we studied the effect of the duration of light exposure, modes of lighting, and circadian interruption on emmetropization in monochromatic light.To achieve this goal, we exposed one-week-old chicks to flickering or steady monochromatic red or blue light for a short (10 days) or long (17 days) duration; other chicks were exposed to white light for 10 days. Refraction and ocular biometry were measured. Activity was measured via a motion detection algorithm and an IR camera. The results showed that in both steady and flickering light, there was a greater increase in axial length and vitreous chamber depth in chicks exposed to red or white light compared to chicks exposed to blue light. With a longer duration of exposure, axial length and vitreous chamber depth differences were no longer observed, except at an intermediate time point. Chicks exposed to red light were more active during the day compared to chicks exposed to blue light. We conclude that our results indicate that with short duration monochromatic light exposure, chicks rely on wavelength defocus to guide emmetropization. With longer exposure from hatching, our results support the notion that responses to wavelength defocus can be transient and that the difference between species may be due to differences in experimental duration and/or interference with circadian activity rhythms.

RNA Splicing Factor Mutations That Cause Retinitis Pigmentosa Result in Circadian Dysregulation.

Circadian clocks regulate multiple physiological processes in the eye, but their requirement for retinal health remains unclear. We previously showed that Drosophila homologs of spliceosome proteins implicated in human retinitis pigmentosa (RP), the most common genetically inherited cause of blindness, have a role in the brain circadian clock. In this study, we report circadian phenotypes in murine models of RP. We found that mice carrying a homozygous H2309P mutation in Pre-mRNA splicing factor 8 (Prpf8) display a lengthened period of the circadian wheel-running activity rhythm. We show also that the daily cycling of circadian gene expression is dampened in the retina of Prpf8-H2309P mice. Surprisingly, molecular rhythms are intact in the eye cup, which includes the retinal pigment epithelium (RPE), even though the RPE is thought to be the primary tissue affected in this form of RP. Downregulation of Prp31, another RNA splicing factor implicated in RP, leads to period lengthening in a human cell culture model. The period of circadian bioluminescence in primary fibroblasts of human RP patients is not significantly altered. Together, these studies link a prominent retinal disorder to circadian deficits, which could contribute to disease pathology.

Agomelatine treatment corrects impaired sleep-wake cycle and sleep architecture and increases MT1 receptor as well as BDNF expression in the hippocampus during the subjective light phase of rats exposed to chronic constant light.

Exposure to chronic constant light (CCL) has a detrimental impact on circadian rhythms of motor activity and sleep/wake cycles. Agomelatine is an atypical antidepressant showing a chronotropic activity. In this study, we explored the role of melatonin (MT) receptors and brain-derived neurotrophic factor (BDNF) in the brain in the mechanism underlying the effects of agomelatine on diurnal variations of motor activity, sleep/wake cycle, and sleep architecture in a rat model of CCL. In Experiment #1, home cage activity was monitored automatically with cameras for a period of 24h. The diurnal rhythm of MT1, MT2 receptors, and BDNF expression in the hippocampus and frontal cortex (FC), was tested using the ELISA test. In Experiment #2, rats were equipped with electroencephalographic (EEG) and electromyographic (EMG) electrodes and recordings were made under basal conditions (12:12 LD cycle + vehicle), LL + vehicle and LL + agomelatine (40mg/kg/day for 21days). The rats exposed to CCL showed an impaired diurnal rhythm of motor activity and sleep/wake cycle with reduced NREM sleep and delta power and increased REM sleep and theta power. The duration and number of episodes of the wake were diminished during the subjective dark phase in this group. The circadian rhythm of MT1 and MT2 receptors and their expression did not change in the hippocampus and FC under CCL exposure, while the BDNF levels in the hippocampus decreased during the subjective light phase. Agomelatine restored the diurnal rhythm of motor activity, disturbed sleep/wake cycle, and sleep architecture, which effect was accompanied by an increase in MT1 receptor and BDNF expression in the hippocampus at 10:00 in CCL rats. These findings support the value of agomelatine as an antidepressant that can adjust circadian homeostasis of motor activity and sleep/wake cycle in a CCL model.

INTEREST GROUP SESSION—SLEEP, CIRCADIAN RHYTHMS AND AGING INTEREST GROUP: SLEEP, PHYSICAL ACTIVITY, AND BRAIN AGING

As the US population ages, the prevalence of Alzheimer’s Disease (AD) and related dementias is expected to increase, making dementia prevention efforts a major public health priority. Impaired sleep and circadian rhythms, along with other lifestyle factors, have emerged as important modifiable disease risk factors—recent studies demonstrate the importance of sleep in preventing the development of key biomarkers for AD/dementia pathology. In this symposium, we will highlight findings on the associations of sleep, circadian rhythm disruptions, and daytime activity patterns on development of cognitive decline and dementia, exploring not only the mechanisms driving these associations, but the potential impact of sleep and lifestyle interventions in promoting healthy brain aging. The symposium consists of four presentations which use data from large national cohort studies. First, we will present analyses on patterns of 24-hour (circadian) activity rhythms (e.g., usual time of day for peak activity, regularity of circadian patterns) and incident dementia risk. The second presentation will present findings pertaining to understanding the link between sleep disturbance and inflammation (a substantial contributor to cognitive aging). The third will examine whether detailed daytime activity patterns associate with imaging-based brain volumes, independent of sleep disturbance. The final presentation will explore whether initiation of sleep disorder treatments may have the potential to change trajectories of cognitive performance as individuals age. Overall, the symposium will highlight the importance of sleep and activity patterns to brain health and stimulate discussion about improving sleep and circadian disruption as a target for dementia prevention efforts.

Sleep Apnea and Sleep Habits: Relationships with Metabolic Syndrome.

Excess visceral adiposity is a primary cause of metabolic syndrome and often results from excess caloric intake and a lack of physical activity. Beyond these well-known etiologic factors, however, sleep habits and sleep apnea also seem to contribute to abdominal obesity and metabolic syndrome: Evidence suggests that sleep deprivation and behaviors linked to evening chronotype and social jetlag affect eating behaviors like meal preferences and eating times. When circadian rest and activity rhythms are disrupted, hormonal and metabolic regulations also become desynchronized, and this is known to contribute to the development of metabolic syndrome. The metabolic consequences of obstructive sleep apnea syndrome (OSAS) also contribute to incident metabolic syndrome. These observations, along with the first sleep intervention studies, have demonstrated that sleep is a relevant lifestyle factor that needs to be addressed along with diet and physical activity. Personalized lifestyle interventions should be tested in subjects with metabolic syndrome, based on their specific diet and physical activity habits, but also according to their circadian preference. The present review therefore focuses (i) on the role of sleep habits in the development of metabolic syndrome, (ii) on the reciprocal relationship between sleep apnea and metabolic syndrome, and (iii) on the results of sleep intervention studies.

A Role of Histone Acetylation in the Regulation of Circadian Rhythm in Ants

Circadian rhythms and associated oscillating gene expression patterns are controlled in many organisms by post-translational modifications of histone proteins. Although epigenetic mechanisms have been suggested to influence key aspects of insect societies, the role of histone modifications in regulating their circadian rhythm has never been studied. Here we ask whether histone acetylation plays a role in adjusting the circadian rhythm in colonies of the ant Temnothorax longispinosus. First, we characterized the circadian activity of 20 colonies by recording the proportion of active ants inside and outside the nest every hour over four days under a 12h:12h light:dark regime. Our analyses revealed that T. longispinosus ants are diurnal and show a clear circadian rhythm in colony-level activity. Second, we tested circadian rhythmicity after shifting the light regime six hours forward to find that the peak activity also moved six hours forward, revealing that colonies rapidly adjust to changes in the light regime. Finally, we investigated whether histone acetylation regulates rhythmicity and its adjustment to light by feeding T. longispinosus colonies with C646, a chemical inhibitor of histone acetyltransferases. Treated colonies lost their circadian rhythmicity, and failed to adjust their activity to the new light regime. These findings suggest a role for histone acetylation in underlying rhythmicity and synchronization of the periodic activity to external cues in T. longispinosus, and implicate epigenetic processes in the regulation of circadian rhythm in a social context.

Tinkering with day length disrupts reproductive diapause

I always feel a little sad when I have to start putting on the lights almost as soon as I get home at the end of the day, but shorter day lengths signify a far more dramatic lifestyle change for many other species. When the number of hours of daylight falls too low, many northern insects place their reproductive systems into suspended animation – known as reproductive diapause – to wait out winter. Some species fine-tune the timing of the switch depending on their latitude, with females from higher latitudes triggering reproductive diapause when the days are longer than those in more southern locations. Yet, how insects synchronize the physiological processes that must be coordinated to harmonise their physiology with the seasons, remained a mystery.With a long-standing interest in how insects predict the onset of winter, Anneli Hoikkala from the University of Jyväskylä, Finland – with colleagues from her university, Oulu University, Finland, and St Andrews, UK – took advantage of the insect's versatility. They artificially evolved populations of Drosophila montana, collected in northern Finland by shortening the amount of daylight experienced by each subsequent generation by 0.5 h to begin unravelling the masterplan that coordinates the flies’ seasonal reproductive off switch. Once they were sure that the diapause trigger had been reprogrammed by the shorter day lengths, the team looked for differences between the new population and flies that had been maintained for generations on a daily schedule of 24 h light, simulating the northern summer.Presenting the new population with days where the number of hours of light varied from 13–21 h over a 24 h period, Hannele Kauranen and Johanna Kinnunen found that 50% of the females went into diapause when they had 17.5 h of light, in contrast to their northerly ancestors, which initiated reproductive diapause at 19.4 h. Then Pekka Lankinen tinkered with the length of the full day – fixing the amount of daylight at 12 h while varying the length of the night from 6 to 72 h – he found that their internal body clocks – circadian rhythms – were not contributing to triggering the flies’ reproductive shut down.Having checked factors that could activate reproductive diapause, the team knew that the wild insects tend to bear cold better as the days draw in, so Anna-Lotta Hiillos measured the temperature at which the evolved flies toppled into a coma when it became too cold. She found that females from the evolved population that had gone into diapause were only able to able to tolerate temperatures down to around –1.8°C while the flies that had experienced normal 24 h days across the generations were able to hold out to –2.2°C; the evolved flies were less cold tolerant. Finally Axel Wiberg and Michael Ritchie analysed the flies’ genome to search for differences that could explain the reproductive diapause shift and found changes in genes involved in the insect's ability to sense light, their hormone signalling, growth and egg development. ‘Overall, our study shows that photoperiodic selection for reproduction under short photoperiods affects diapause-associated traits without disrupting the central clock network generating circadian rhythms in fly locomotor activity’, says Kauranen.

Rhythmic Release of Corticosterone Induces Circadian Clock Gene Expression in the Cerebellum

Neurons of the cerebellar cortex contain a circadian oscillator, with circadian expression of clock genes being controlled by the master clock of the suprachiasmatic nucleus (SCN). However, the signaling pathway connecting the SCN to the cerebellum is unknown. Glucocorticoids exhibit a prominent SCN-dependent circadian rhythm, and high levels of the glucocorticoid receptor have been reported in the cerebellar cortex; we therefore hypothesized that glucocorticoids may control the rhythmic expression of clock genes in the cerebellar cortex. We here applied a novel methodology by combining the electrolytic lesion of the SCN with implantation of a micropump programmed to release corticosterone in a circadian manner mimicking the endogenous hormone profile. By use of this approach, we were able to restore the corticosterone rhythm in SCN-lesioned male rats. Clock gene expression in the cerebellum was abolished in rats with a lesioned SCN, but exogenous corticosterone restored the daily rhythm in clock gene expression in the cerebellar cortex, as revealed by quantitative real-time PCR and radiochemical in situ hybridization for the detection of the core clock genes Per1, Per2, and Arntl. On the contrary, exogenous hormone did not restore circadian rhythms in body temperature and running activity. RNAscope in situ hybridization further revealed that the glucocorticoid receptor colocalizes with clock gene products in cells of the cerebellar cortex, suggesting that corticosterone exerts its actions by binding directly to receptors in neurons of the cerebellum. However, rhythmic clock gene expression in the cerebellum was also detectable in adrenalectomized rats, indicating that additional control mechanisms exist. These data show that the cerebellar circadian oscillator is influenced by SCN-dependent rhythmic release of corticosterone.