Entrainment Of Circadian Rhythms Research Articles

Evolutionary History of the Photolyase/Cryptochrome Superfamily in Eukaryotes

BackgroundPhotolyases and cryptochromes are evolutionarily related flavoproteins, which however perform distinct physiological functions. Photolyases (PHR) are evolutionarily ancient enzymes. They are activated by light and repair DNA damage caused by UV radiation. Although cryptochromes share structural similarity with DNA photolyases, they lack DNA repair activity. Cryptochrome (CRY) is one of the key elements of the circadian system in animals. In plants, CRY acts as a blue light receptor to entrain circadian rhythms, and mediates a variety of light responses, such as the regulation of flowering and seedling growth.ResultsWe performed a comprehensive evolutionary analysis of the CRY/PHR superfamily. The superfamily consists of 7 major subfamilies: CPD class I and CPD class II photolyases, (6–4) photolyases, CRY-DASH, plant PHR2, plant CRY and animal CRY. Although the whole superfamily evolved primarily under strong purifying selection (average ω = 0.0168), some subfamilies did experience strong episodic positive selection during their evolution. Photolyases were lost in higher animals that suggests natural selection apparently became weaker in the late stage of evolutionary history. The evolutionary time estimates suggested that plant and animal CRYs evolved in the Neoproterozoic Era (~1000–541 Mya), which might be a result of adaptation to the major climate and global light regime changes occurred in that period of the Earth’s geological history.

Pigment-dispersing factor signaling in the circadian system of Caenorhabditis elegans.

The neuropeptide pigment-dispersing factor (PDF) is important for the generation and entrainment of circadian rhythms in the fruitfly Drosophila melanogaster. Recently two pdf homologs, pdf-1 and pdf-2, and a PDF receptor, pdfr-1, have been found in Caenorhabditis elegans and have been implicated in locomotor activity. In this work, we have studied the role of the PDF neuropeptide in the circadian system of C. elegans and found that both pdf-1 and pdf-2 mutants affect the normal locomotor activity outputs. In particular, loss of pdf-1 induced circadian arrhythmicity under both light-dark (LD) and constant dark (DD) conditions. These defects can be rescued by a genomic copy of the pdf-1 locus. Our results indicate that PDF-1 is involved in rhythm generation and in the synchronization to LD cycles, as rhythmic patterns of activity rapidly disappear when pdf-1 mutants are recorded under both entrained and free-running conditions. The role of PDF-2 and the PDF receptors is probably more complex and involves the interaction between the two pdf paralogues found in the nematode.

Comparison of light, food, and temperature as environmental synchronizers of the circadian rhythm of activity in mice

Although entrainment (and masking) of circadian rhythms by light has been extensively studied, much less attention has been given to other environmental cycles that can modulate circadian rhythms in mammals. In this study in mice, the entraining strength of different environmental cycles was compared. Running-wheel activity was monitored before, after, and while the animals were under one of four environmental cycles: a full light-dark cycle with 12 h of light and 12 h of darkness each day, a cycle of 1 h of light per day, a cycle of food availability consisting of 80% of the baseline free-feeding amount presented once a day, and an ambient temperature cycle consisting of 23 h at 24 °C and 1 h at 12 °C each day. Four measures of zeitgeber strength were used: percentage of animals that entrained, rhythm robustness in the entrained state, stability of activity onsets, and stability of acrophases. The results indicate that, at least in mice, a full light-dark cycle is the most powerful modulator of the circadian rhythm of locomotor activity, as a consequence of both entrainment and masking. When entrainment alone is considered, temperature seems to be as strong a modulator as light, while food restriction is a weaker modulator and affects primarily a food-anticipatory component of the activity rhythm.

Glutamate-Dependent BMAL1 Regulation in Cultured Bergmann Glia Cells.

Glutamate, the major excitatory amino acid, activates a wide variety of signal transduction cascades. This neurotransmitter is involved in photic entrainment of circadian rhythms, which regulate physiological and behavioral functions. The circadian clock in vertebrates is based on a transcription-translation feedback loop in which Brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like protein 1 (BMAL1) acts as transcriptional activator of others clock genes. This protein is expressed in nearly all suprachiasmatic nucleus neurons, as well as in the granular layer of the cerebellum. In this context, we decided to investigate the role of glutamate in the molecular mechanisms involved in the processes of transcription/translation of BMAL1 protein. To this end, primary cultures of chick cerebellar Bergmann glial cells were stimulated with glutamatergic ligands and we found that BMAL1 levels increased in a dose- and time dependent manner. Additionally, we studied the phosphorylation of serine residues in BMAL1 under glutamate stimulation and we were able to detect an increase in the phosphorylation of this protein. The increased expression of BMAL1 is most probably the result of a stabilization of the protein after it has been phosphorylated by the cyclic AMP-dependent protein kinase and/or the Ca(2+)/diacylglycerol dependent protein kinase. The present results strongly suggest that glutamate participates in regulating BMAL1 in glial cells and that these cells might prove to be important in the control of circadian rhythms in the cerebellum.

Persistence, entrainment, and function of circadian rhythms in polar vertebrates.

Polar organisms must cope with an environment that periodically lacks the strongest time-giver, or zeitgeber, of circadian organization-robust, cyclical oscillations between light and darkness. We review the factors influencing the persistence of circadian rhythms in polar vertebrates when the light-dark cycle is absent, the likely mechanisms of entrainment that allow some polar vertebrates to remain synchronized with geophysical time, and the adaptive function of maintaining circadian rhythms in such environments.

Green-sensitive opsin is the photoreceptor for photic entrainment of an insect circadian clock.

IntroductionEntrainment to light cycle is a prerequisite for circadian rhythms to set daily physiological events to occur at an appropriate time of day. In hemimetabolous insects, the photoreceptor molecule for photic entrainment is still unknown. Since the compound eyes are the only circadian photoreceptor in the cricket Gryllus bimaculatus, we have investigated the role of three opsin genes expressed there, opsin-Ultraviolet (opUV), opsin-Blue (opB), and opsin-Long Wave (opLW) encoding a green-sensitive opsin in photic entrainment.ResultsA daily rhythm was detected in mRNA expressions of opB and opLW but not of opUV gene. When photic entrainment of circadian locomotor rhythms was tested after injection of double-stranded RNA (dsRNA) of three opsin genes, no noticeable effects were found in opUV RNAi and opB RNAi crickets. In opLW RNAi crickets, however, some crickets lost photic entrainability and the remaining crickets re-entrained with significantly longer transient cycles to a phase-advanced light–dark cycle as compared to control crickets. Crickets often lost entrainability when treated doubly with dsRNAs of two opsin genes including opLW.ConclusionThese results show that green-sensitive OpLW is the major circadian photoreceptor molecule for photic entrainment of locomotor rhythms in the cricket G. bimaculatus. Our finding will lead to further investigation of the photic entrainment mechanism at molecular and cellular levels, which still remains largely unknown.Electronic supplementary materialThe online version of this article (doi:10.1186/s40851-015-0011-6) contains supplementary material, which is available to authorized users.

Entrainment of Cellular Circadian Rhythms in Lactuca sativa L. Leaf by Spatially Controlled Illuminations

Plant circadian system works autonomously and responds to various environmental information in cellular level. Conventional studies on controlling of the plant circadian system, however, have not thoroughly considered in cellular level yet. In this study, we investigated spatiotemporal dynamics of cellular circadian rhythms of clock gene CCA1 in leaves that were controlled by the projector lightings in a transgenic lettuce strain AtCCA1::LUC using a bioluminescence imaging. We have succeeded to control the cellular circadian rhythms in the both case of LCD and laser projectors with 24 or 26 h periods of light-dark cycles. Although light intensity of the laser projector was very small to a required light intensity for growth of lettuces, the circadian rhythm was entrained with high sensitivity for illumination. Our results motivate experimental and theoretical studies of circadian control and development for the highly functional lighting technology in plant productions.

Tasimelteon

To examine the efficacy of tasimelteon for the treatment of non-24-hour sleep-wake disorder using evidence from controlled clinical trials. Citations in Google Scholar and PubMed from January 1, 2008, to May 31, 2014, were identified using tasimelteon as the search term. Results were limited to human trials published in English. Trials that compared tasimelteon with placebo were included. A phase II trial (n = 39) evaluated the effects of tasimelteon versus placebo on improvements in sleep efficiency and the ability to shift circadian rhythms over 3 days. Significant shifts in circadian rhythm were only observed for 100-mg tasimelteon. A phase III trial (n = 412) evaluated the effects of tasimelteon versus placebo on assessment of latency to persistent sleep and wake after sleep onset; significant advantages were observed in tasimelteon recipients. The SET (Safety and Efficacy of Tasimelteon) trial (n = 84) enrolled blind men and women with Non-24. They received placebo or tasimelteon 20 mg daily. Tasimelteon recipients had significantly (P = 0.0025) better entrainment and N24CRS scores. The RESET (Randomized Withdrawal Study of the Efficacy and Safety of Tasimelteon) trial (n = 20) enrolled entrained participants from the SET trial who received 20 mg of tasimelteon or placebo daily for 8 weeks. The primary objective was to evaluate the maintenance of effect of tasimelteon to entrain circadian rhythms. Tasimelteon was associated with significantly (P = 0.0055) greater entrainment than placebo. Tasimelteon improves sleep initiation and maintenance in patients with Non-24 who have a shift in endogenous circadian rhythms. However, the cost of this agent limits its use.

The Relationship Between Light Exposure and Sleep, Fatigue, and Depression in Cancer Outpatients

Light is an important cue for the entrainment of circadian rhythms, which can be related to sleep quality, fatigue, and depression in cancer patients. The purpose of this study was to determine the effects of light exposure on sleep quality, fatigue, and depression in cancer patients, to test whether the effect of light exposure on sleep quality, fatigue, and depression was mediated by the other 2 symptoms. This was a cross-sectional study for which we recruited 163 cancer outpatients. For 3 consecutive days, they wore an Actiwatch to measure light exposure. Instruments included the Pittsburgh Sleep Quality Index-Taiwan form, the Brief Fatigue Inventory-Taiwan form, and the Beck Depression Inventory II-Taiwan version. The results indicated that the Pittsburgh Sleep Quality Index-Taiwan form score was significantly and negatively correlated with minutes of light exposure (MLE) of 1000 lux or greater (r = -0.61, P < .001) and the intensity of light exposure under activity (r = -0.59, P < .001). Fatigue was negatively correlated with MLE (r = -0.18, P = .03). Depression was also negatively correlated with MLE and intensity of light exposure (both r = -0.18, P = .02). Most important, the effect of light exposure on sleep quality, fatigue, and depression was mediated by the other 2 symptoms. Light exposure appeared to be a shared factor for the co-occurrence of fatigue, sleep disturbances, and depression. Light exposure has great potential for improving sleep quality as well as ameliorating fatigue and depression in cancer outpatients.

Intergeniculate leaflet lesions result in differential activation of brain regions following the presentation of photic stimuli in Nile grass rats

The intergeniculate leaflet (IGL) plays an important role in the entrainment of circadian rhythms and the mediation of acute behavioral responses to light (i.e., masking). Recently, we reported that IGL lesions in diurnal grass rats result in a reversal in masking responses to light as compared to controls. Here, we used Fos as a marker of neural activation to examine the mechanisms by which the IGL may influence this masking effect of light in grass rats. Specifically, we examined the patterns of Fos activation in retinorecipient areas and in brain regions that receive IGL inputs following 1-h light pulses given during the early night in IGL-lesioned and sham-operated grass rats. Three patterns emerged: (1) IGL lesions had no effect on the Fos response to light, (2) IGL lesions resulted in a reversal in Fos responses to light, and (3) IGL lesions resulted in a lack of a Fos response to light. Of specific interest were the suprachiasmatic nucleus (SCN) and the olivary pretectal nucleus (OPT), both of which are retinorecipient and connect reciprocally with the IGL. Light-induced Fos expression in the SCN was unaffected by IGL lesions, whereas the OPT exhibited a significant reduction in Fos expression following a light pulse in animals with IGL lesions. Altogether, our results suggest that the OPT, but not the SCN, exhibits a reversal in Fos responses to light following IGL lesions that reverse masking responses in diurnal grass rats. Our results suggest that interconnections between the IGL and downstream brain areas (e.g., OPT) may play a role in determining the direction of the behavioral response to light.

Evaluation of the steric impact of flavin adenine dinucleotide in Drosophila melanogaster cryptochrome function

Photoreceptors are crucial components for circadian rhythm entrainment in animals, plants, fungi and cyanobacteria. Cryptochromes (CRYs) are flavin adenine dinucleotide (FAD) containing photoreceptors, and FAD is responsible for signal transduction, in contrast to photolyases where it promotes DNA-damage repair. In this work, we investigated an alternative role for FAD in CRY. We analyzed the Drosophila melanogaster CRY crystal structure by means of molecular dynamics, elucidating how this large co-factor within the receptor could be crucial for CRY structural stability. The co-factor appears indeed to improve receptor motility, providing steric hindrance. Moreover, multiple sequence alignments revealed that conserved motifs in the C-terminal tail could be necessary for functional stability.

Sugars take a central position in plant growth, development and, stress responses. A focus on apical dominance.

Sugars take a central position in plant growth, development and, stress responses. A focus on apical dominance.

Role of p53 in the entrainment of mammalian circadian behavior rhythms

p53 protein plays a role for control of cell proliferation and the induction of apoptosis in normal cells. However, its role in the circadian rhythms that control many physiological functions including locomotor behavior remains unknown. The present study examined the locomotors activity rhythms of mice which have homozygous mutations of p53 gene. The period of drinking activity rhythms in p53 knockout (p53 KO) mice became unstable under constant dark. Light pulse causes a big phase shifts at CT15.5-17, when p53 mRNA expression peaks in the suprachiasmatic nucleus (SCN). Furthermore, photic entrainment of p53 KO mice is unusual under light-dark conditions. These findings suggest that p53 is involved in entrainment of the circadian behavioral rhythm.

Wiring the retinal circuits activated by light during early development

BackgroundLight information is sorted by neuronal circuits to generate image-forming (IF) (interpretation and tracking of visual objects and patterns) and non-image-forming (NIF) tasks. Among the NIF tasks, photic entrainment of circadian rhythms, the pupillary light reflex, and sleep are all associated with physiological responses, mediated mainly by a small group of melanopsin-expressing retinal ganglion cells (mRGCs). Using Xenopus laevis as a model system, and analyzing the c-fos expression induced by light as a surrogate marker of neural activity, we aimed to establish the developmental time at which the cells participating in both systems come on-line in the retina.ResultsWe found that the peripheral retina contains 80% of the two melanopsin-expressing cell types we identified in Xenopus: melanopsin-expressing horizontal cells (mHCs; opn4m+/opn4x+/Prox1+) and mRGCs (2.7% of the total RGCs; opn4m+/opn4x+/Pax6+/Isl1), in a ratio of 6:1. Only mRGCs induced c-fos expression in response to light. Dopaminergic (tyrosine hydroxylase-positive; TH+) amacrine cells (ACs) may be part of the melanopsin-mediated circuit, as shown by preferential c-fos induction by blue light. In the central retina, two cell types in the inner nuclear layer (INL) showed light-mediated induction of c-fos expression [(On-bipolar cells (Otx2+/Isl1+), and a sub-population of ACs (Pax6−/Isl1−)], as well as two RGC sub-populations (Isl1+/Pax6+ and Isl1+/Pax6−). Melanopsin and opsin expression turned on a day before the point at which c-fos expression could first be activated by light (Stage 37/38), in cells of both the classic vision circuit, and those that participate in the retinal component of the NIF circuit. Key to the classic vision circuit is that the component cells engage from the beginning as functional ‘unit circuits’ of two to three cells in the INL for every RGC, with subsequent growth of the vision circuit occurring by the wiring in of more units.ConclusionsWe identified melanopsin-expressing cells and specific cell types in the INL and the RGC layer which induce c-fos expression in response to light, and we determined the developmental time when they become active. We suggest an initial formulation of retinal circuits corresponding to the classic vision pathway and melanopsin-mediated circuits to which they may contribute.

Daily exposure to a running wheel entrains circadian rhythms in mice in parallel with development of an increase in spontaneous movement prior to running-wheel access

Entrainment of circadian behavior rhythms by daily exposure to a running wheel was examined in mice under constant darkness. Spontaneous movement was individually monitored for more than 6 mo by a thermal sensor. After establishment of steady-state free running, mice were placed in a different cage equipped with a running-wheel for 3 h once per day at 6 AM. The daily exchange was continued for 80 days. The number of wheel revolutions during exposure to the running wheel was also measured simultaneously with spontaneous movement. In 13 out of 17 mice, circadian behavior rhythm was entrained by daily wheel exposure, showing a period indistinguishable from 24 h. The entrainment occurred in parallel with an increase in spontaneous movement immediately prior to the daily wheel exposure. A similar preexposure increase was observed in only one of four nonentrained mice. The preexposure increase appeared in 19.5 days on average after the start of daily wheel exposure and persisted for 36 days on average after the termination of the exposure schedule. The preexposure increase was detected only when daily wheel exposure came into the activity phase of the circadian behavior rhythm, which was accompanied by an increase in the number of wheel revolutions. These findings indicate that a novel oscillation with a circadian period is induced in mice by daily exposure to a running wheel at a fixed time of day and suggest that the oscillation is involved in the nonphotic entrainment of circadian rhythms in spontaneous movement.

Photosynthetic entrainment of the Arabidopsis thaliana circadian clock

Circadian clocks provide a competitive advantage in an environment that is heavily influenced by the rotation of the Earth, by driving daily rhythms in behaviour, physiology and metabolism in bacteria, fungi, plants and animals. Circadian clocks comprise transcription-translation feedback loops, which are entrained by environmental signals such as light and temperature to adjust the phase of rhythms to match the local environment. The production of sugars by photosynthesis is a key metabolic output of the circadian clock in plants. Here we show that these rhythmic, endogenous sugar signals can entrain circadian rhythms in Arabidopsis thaliana by regulating the gene expression of circadian clock components early in the photoperiod, thus defining a 'metabolic dawn'. By inhibiting photosynthesis, we demonstrate that endogenous oscillations in sugar levels provide metabolic feedback to the circadian oscillator through the morning-expressed gene PSEUDO-RESPONSE REGULATOR 7 (PRR7), and we identify that prr7 mutants are insensitive to the effects of sucrose on the circadian period. Thus, photosynthesis has a marked effect on the entrainment and maintenance of robust circadian rhythms in A. thaliana, demonstrating that metabolism has a crucial role in regulation of the circadian clock.

Neonatal monosodium glutamate treatment counteracts circadian arrhythmicity induced by phase shifts of the light–dark cycle in female and male Siberian hamsters

Studies of rats and voles suggest that distinct pathways emanating from the anterior hypothalamic-retrochiasmatic area and the mediobasal hypothalamic arcuate nucleus independently generate ultradian rhythms (URs) in hormone secretion and behavior. We evaluated the hypothesis that destruction of arcuate nucleus (ARC) neurons, in concert with dampening of suprachiasmatic nucleus (SCN) circadian rhythmicity, would compromize the generation of ultradian rhythms (URs) of locomotor activity. Siberian hamsters retain-->of both sexes treated neonatally with monosodium glutamate (MSG) that destroys ARC neurons were subjected in adulthood to a circadian disrupting phase-shift protocol (DPS) that produces SCN arrhythmia. MSG treatments induced hypogonadism and obesity, retain-->and markedly reduced the size of the optic chiasm and optic nerves. MSG-treated hamsters exhibited normal entrainment to the light–dark cycle, but MSG treatretain-->ment counteracted the circadian arrhythmicity induced by the DPS protocol: only 6% of retain-->MSG-treated hamsters exhibited circadian arrhythmia, whereas 50% of control hamsters were circadian disrupted. In MSG-treated hamsters that retained circadian rhythmicity after DPS treatment, quantitative parameters of URs appeared normal, but in the two MSG-treated hamsters that became circadian arrhythmic after DPS, both dark-phase and light-phase URs were abolished. Although preliminary, these data are consistent with reports in voles suggesting that the combined disruption of SCN and ARC function impairs the expression of behavioral URs. The data also suggest that light thresholds for entrainment of circadian rhythms may be lower than those required to disrupt circadian organization.

Bacterial Bioluminescence Regulates Expression of a Host Cryptochrome Gene in the Squid-Vibrio Symbiosis

ABSTRACTThe symbiosis between the squid Euprymna scolopes and its luminous symbiont, Vibrio fischeri, is characterized by daily transcriptional rhythms in both partners and daily fluctuations in symbiont luminescence. In this study, we sought to determine whether symbionts affect host transcriptional rhythms. We identified two transcripts in host tissues (E. scolopes cry1 [escry1] and escry2) that encode cryptochromes, proteins that influence circadian rhythms in other systems. Both genes cycled daily in the head of the squid, with a pattern similar to that of other animals, in which expression of certain cry genes is entrained by environmental light. In contrast, escry1 expression cycled in the symbiont-colonized light organ with 8-fold upregulation coincident with the rhythms of bacterial luminescence, which are offset from the day/night light regime. Colonization of the juvenile light organ by symbionts was required for induction of escry1 cycling. Further, analysis with a mutant strain defective in light production showed that symbiont luminescence is essential for cycling of escry1; this defect could be complemented by presentation of exogenous blue light. However, blue-light exposure alone did not induce cycling in nonsymbiotic animals, but addition of molecules of the symbiont cell envelope to light-exposed animals did recover significant cycling activity, showing that light acts in synergy with other symbiont features to induce cycling. While symbiont luminescence may be a character specific to rhythms of the squid-vibrio association, resident microbial partners could similarly influence well-documented daily rhythms in other systems, such as the mammalian gut.

Cognitive Performance as a Zeitgeber: Cognitive Oscillators and Cholinergic Modulation of the SCN Entrain Circadian Rhythms

The suprachiasmatic nucleus (SCN) is the primary circadian pacemaker in mammals that can synchronize or entrain to environmental cues. Although light exerts powerful influences on SCN output, other non-photic stimuli can modulate the SCN as well. We recently demonstrated that daily performance of a cognitive task requiring sustained periods of attentional effort that relies upon basal forebrain (BF) cholinergic activity dramatically alters circadian rhythms in rats. In particular, normally nocturnal rats adopt a robust diurnal activity pattern that persists for several days in the absence of cognitive training. Although anatomical and pharmacological data from non-performing animals support a relationship between cholinergic signaling and circadian rhythms, little is known about how endogenous cholinergic signaling influences SCN function in behaving animals. Here we report that BF cholinergic projections to the SCN provide the principal signal allowing for the expression of cognitive entrainment in light-phase trained animals. We also reveal that oscillator(s) outside of the SCN drive cognitive entrainment as daily timed cognitive training robustly entrains SCN-lesioned arrhythmic animals. Ablation of the SCN, however, resulted in significant impairments in task acquisition, indicating that SCN-mediated timekeeping benefits new learning and cognitive performance. Taken together, we conclude that cognition entrains non-photic oscillators, and cholinergic signaling to the SCN serves as a temporal timestamp attenuating SCN photic-driven rhythms, thereby permitting cognitive demands to modulate behavior.

Entrainment of Circadian Rhythms to Environmental cycles in Lactuca sativa L. - Characteristics of Circadian Rhythms in Lettuce -

The circadian clock that exists in terrestrial organisms to trigger various physiological phenomena within a period of approximately 24 hours. This approximate time range of 24 hr periodicity is called the “circadian rhythm”. Recently, the studies of circadian rhythms suggest that the control of circadian rhythm can contribute to improvement of the productivity of plant growth (called circadian resonance). Therefore, it is necessary to investigate the features of circadian rhythm and to search for optimal light conditions that best suit plant cultivation. In this study, we analyzed the characterization of circadian rhythms through a luciferase luminescence assay in Lactuca sativa L.