24-hr Rhythm Research Articles

CLOCK evolved in cnidaria to synchronize internal rhythms with diel environmental cues

CLOCK evolved in cnidaria to synchronize internal rhythms with diel environmental cues

CLOCK evolved in cnidaria to synchronize internal rhythms with diel environmental cues.

The circadian clock enables anticipation of the day/night cycle in animals ranging from cnidarians to mammals. Circadian rhythms are generated through a transcription-translation feedback loop (TTFL or pacemaker) with CLOCK as a conserved positive factor in animals. However, CLOCK's functional evolutionary origin and mechanism of action in basal animals are unknown. In the cnidarian Nematostella vectensis, pacemaker gene transcript levels, including NvClk (the Clock ortholog), appear arrhythmic under constant darkness, questioning the role of NvCLK. Utilizing CRISPR/Cas9, we generated a NvClk allele mutant (NvClkΔ), revealing circadian behavior loss under constant dark (DD) or light (LL), while maintaining a 24 hr rhythm under light-dark condition (LD). Transcriptomics analysis revealed distinct rhythmic genes in wild-type (WT) polypsunder LD compared to DD conditions. In LD, NvClkΔ/Δ polyps exhibited comparable numbers of rhythmic genes, but were reduced in DD. Furthermore, under LD, the NvClkΔ/Δ polyps showed alterations in temporal pacemaker gene expression, impacting their potential interactions. Additionally, differential expression of non-rhythmic genes associated with cell division and neuronal differentiation was observed. These findings revealed that a light-responsive pathway can partially compensate for circadian clock disruption, and that the Clock gene has evolved in cnidarians to synchronize rhythmic physiology and behavior with the diel rhythm of the earth's biosphere.

CIRCADIAN TIMING OF THE IMMUNOMETABOLIC RESPONSE AFFECTS ALZHEIMER’S DISEASE PATHOLOGY

Abstract Though the predominant model of the biological mechanisms underlying ADRDs is based on the beta-amyloid (Aβ) hypothesis, evidence suggests that inflammation from resident immune cells is also a key component of the development of ADRD pathophysiology. A major biological regulator of inflammation is the circadian clock, the 24-hour molecular timekeeper that broadly regulates gene expression throughout mammalian tissues to synchronize biology to the Earth’s day/night cycle. Concordantly, chronic disruption of the circadian clock (CD) increases the risk for and severity of ADRDs. Our research has revealed that the circadian clock times metabolism, with the clock timing mitochondrial division which in turn times the response of mammalian macrophages to ADRD pathological factors. We show that subunits of the enzyme NOX2, a driver in the creation of reactive oxygen species (ROS) that uses metabolites to impart inflammation, are driven to oscillate in a 24 hr rhythm by the circadian clock in macrophages and microglia. Notably, oscillations in these NOX2 subunits are dysregulated when an organism undergoes CD, leading to an increase in the levels of ROS released by macrophages and microglia and elevating overall levels of inflammation. Given the apparent interconnection between inflammation, circadian rhythms, and ADRDs, an understanding of the circadian timing of the immune system could be exploited to develop treatments that alleviate ADRD symptoms, contribute to a potential cure, and prevent a population-wide increase in neurodegeneration due to a societal surge in CD.

Abstract 15606: Effectiveness and Safety of the Dual Epicardial & Endocardial Procedure (DEEP) Approach for Treatment of Subjects With Persistent or Long Standing Persistent Atrial Fibrillation (PersAF/LSPAF) With Radiofrequency Ablation

Background: A collaborative approach between Electrophysiologists (EP) and Cardiothoracic Surgeons (CTS) to effectively target pulmonary veins (PVs) and substrate beyond PVs may improve outcomes for persistent and longstanding persistent AF (PersAF/LSPerAF). Hypothesis: A minimally invasive hybrid approach of bilateral thoracoscopic epicardial ablation and left atrial appendage exclusion (LAAE) with endocardial mapping/ablation (Hybrid approach) is safe and effective to treat advanced AF patients who have failed medical therapy. Aim: DEEP (NCT02393885) aims to establish safety and effectiveness of a Bipolar Radiofrequency (RF) System in a Hybrid approach to treat PersAF/LSPerAF. Methods: DEEP is a prospective, international, single arm trial at 17 sites. Key eligibility: adults with drug refractory PersAF/LSPerAF, left atrial diameter (LAD) ≤5.5cm, failed class I/III AAD, and ≤2 previous failed endocardial catheter ablations (CA). Epicardial surgical ablation included PV isolation, roof and floor lines (posterior LA box), left superior PV to LAA lesion, ganglionic plexi and Ligament of Marshall ablation and LAAE. CA followed 91-121 D post epicardial procedure. After 90 D blanking and 90 D AAD optimization periods, 24-hr rhythm monitoring and ECG were performed 6 and 12 M post CA with symptom driven monitoring between. Primary effectiveness was defined as freedom from atrial arrhythmia (>30 sec) absent new/increased dose of previously failed AAD through 12 M. Safety was device/procedure-related SAEs within 30 D of epicardial ablation and 7 D of CA in all who received anesthesia. Results: Ninety patients were enrolled in 2015-2020, 83.3% PersAF, 16.7% LSPerAF, mean age 63.4±7.74 yrs, 83.3% male, mean BMI 29.9, CHAD2DS2-VASc median 2.0 (1.0, 3.0), 48% failed CA, median AF duration 3.8 yrs, mean LAD 4.5cm. Primary effectiveness 70.6% (60/85; 95% CI 60.9%, 80.3%, p=0.0232) and freedom from AF through 12 M 78.8% (p=0.0002). The adverse event rate was 6.7% (6/90); equal in epi- and endocardial cohort. Both primary endpoints met prespecified success criteria. Conclusion: A collaborative approach between EP and CTS to Hybrid ablation is effective for PersAF/LSerPAF when benefit-risk is deemed favorable, given limited alternative treatments.

Diurnal oscillations of MRI metrics in the brains of male participants

Regulation of biological processes according to a 24-hr rhythm is essential for the normal functioning of an organism. Temporal variation in brain MRI data has often been attributed to circadian or diurnal oscillations; however, it is not clear if such oscillations exist. Here, we provide evidence that diurnal oscillations indeed govern multiple MRI metrics. We recorded cerebral blood flow, diffusion-tensor metrics, T1 relaxation, and cortical structural features every three hours over a 24-hr period in each of 16 adult male controls and eight adult male participants with bipolar disorder. Diurnal oscillations are detected in numerous MRI metrics at the whole-brain level, and regionally. Rhythmicity parameters in the participants with bipolar disorder are similar to the controls for most metrics, except for a larger phase variation in cerebral blood flow. The ubiquitous nature of diurnal oscillations has broad implications for neuroimaging studies and furthers our understanding of the dynamic nature of the human brain.

Is there an association between socioeconomic status and the degree of diurnal variation in heart rate?

BackgroundDisruption in circadian rhythms is associated with cardiovascular disease and may play a role in socioeconomic differences in cardiovascular disease prevalence. However, it is unclear whether low SES is associated with a lower diurnal rhythm in autonomic activity markers. We investigated the association between SES and the amplitude of the daily fluctuation of heart rate. MethodsWe included data of 450 participants of a HELIUS sub-study in Amsterdam, the Netherlands. Participants wore an Actiheart monitor (CamNtech), a chest-worn monitor which measures heart rate every 15 s for several days. Cosinor analysis was performed on the time series of heart rate within each participant. We analyzed the association between the cosinor parameters (amplitude, midline and peak time of the diurnal HR rhythm) and SES indicators (education, occupational class and a proxy of income) in multivariate linear regression models, adjusting for age, sex and ethnicity. ResultsThere was a clear diurnal rhythm in the average heart rates, with a peak between noon and 18:00 and a trough between 04:00 and 06:00. This rhythm was present for all categories of education, occupation and income proxy. The estimates for the cosinor parameters did not differ consistently and significantly between categories of education, occupation or income proxy. ConclusionsWe did not find any consistent evidence to support our hypothesis of a diminished amplitude in the diurnal variation of heart rate in individuals with lower SES. Future studies should explore SES differences in the diurnal variation in markers of autonomic activity other than heart rate.

The role of natural light rhythm in the development of desynchronosis in the conditions of rotational shiftwork in the Arctic

Purpose. To study the effects of a natural light cycle on circadian rhythms of blood pressure (BP) and heart rate conditions of rotational shiftwork in the Far North. Material and Methods . Data of 24-h BP monitoring were analyzed in 373 male patients with hypertension stage II monthly round-trip sojourns to the Arctic compared with a similar group of 144 patients living in moderate climate (Tyumen, 57 N). The standard and chronobiological parameters of 24-h BP monitoring were analyzed in 93 randomly selected patients of the Far North group and 64 patients of the Tyumen group. The 24-h BP profile, circadian indices of systolic and diastolic BP, percentage contribution value, rhythm amplitude, acrophase, and diurnal mean value of 24-h BP rhythm were studied during the seasons of the year. Results. The circadian rhythms of HR and BP in hypertensive patients in the conditions of rotational shiftwork in the Arctic showed the signs of internal desynchronosis and significantly differed from those in Tyumen patients independently of a season. The lack of natural light in the Far North during the polar day and polar night resulted in the flattened curves of circadian BP and HR rhythms in the hypertensive patients. Other major differences consisted in the low-amplitude profile of the spectrum and the loss of 24-h component in this group. The seasonal changes in HR in the comparison group were insignificant unlike those in the Far North group, which showed maximum flattening of HR rhythm during the polar day and polar night. Winter season (polar night) was the most adverse for the main group of patients in regard to their 24-h BP profile, which was characterized by the maximum degree of circadian rhythm flattening and the predominance of high-frequency oscillations in the spectrum. Conclusions. The development of circadian and seasonal desynchronosis of the HR and BP rhythms in hypertensive patients in the conditions of rotational shiftwork in the Arctic was caused not only by the labour characteristics and the climatic factors, but also by the natural light rhythmicity in the high latitude.

Twenty-four-hour motor activity and body temperature patterns suggest altered central circadian timekeeping in Smith-Magenis syndrome, a neurodevelopmental disorder.

Smith-Magenis syndrome (SMS) is a contiguous gene syndrome linked to interstitial microdeletion, or mutation of RAI1, within chromosome 17p11.2. Key behavioral features of SMS include intellectual disability, sleep-disturbances, maladaptive, aggressive and self-injurious behaviors, hyperactivity, and sudden changes in mood. A distinguishing feature of this syndrome is an inverted pattern of melatonin characterized by elevated daytime and low nighttime melatonin levels. As the central circadian clock controls the 24-hr rhythm of melatonin, we hypothesized that the clock itself may contribute to the disrupted pattern of melatonin and sleep. In this report, 24-hr patterns of body temperature, a surrogate marker of clock-timing, and continuous wrist activity were collected to examine the links between body temperature, sleep behavior, and the circadian clock. In addition, age-dependent changes in sleep behavior were explored. Actigraphy-estimated sleep time for SMS was 1 hr less than expected across all ages studied. The timing of the 24-hr body temperature (Tb-24) rhythm was phase advanced, but not inverted. Compared to sibling (SIB) controls, the SMS group had less total night sleep, lower sleep efficiency, earlier sleep onset, earlier final awake times, increased waking after sleep onset (WASO), and increased daytime nap duration. The timing of wake onset varied with age, providing evidence of ongoing developmental sleep changes from childhood through adolescence. Clarification of the circadian and developmental factors that contribute to the disrupted and variable sleep patterns in this syndrome will be helpful in identifying more effective individualized treatments.

Effect of Atropine on Adrenergic Responsiveness of Erythrocyte and Heart Rhythm Variability in Outbred Rats with Stimulation of the Central Neurotransmitter Systems

Single injection of muscarinic cholinoceptor blocker atropine (1 mg/kg) to outbred male rats reduced β-adrenergic responsiveness of erythrocytes (by 2.2 times) and the content of epinephrine granules on erythrocytes (by 1.5 times), significantly increased HR and rigidity of the heart rhythm, and manifold decreased the power of all spectral components of heart rhythm variability. Stimulation of the central neurotransmitter systems increased β-adrenergic responsiveness of erythrocytes (by 15-26%), decreased the number of epinephrine granules on erythrocytes (by 25-40%), and increased HR and cardiac rhythm intensity. These changes were most pronounced after stimulation of the serotoninergic system. Administration of atropine against the background of activation of central neurotransmitter systems did not decrease β-adrenergic responsiveness of erythrocytes (this parameter remained at a stably high level and even increased during stimulation of the dopaminergic system), but decreased the number of epinephrine granules on erythrocytes, increased HR, and dramatically decreased the power of all components of heart rhythm variability spectrum. The response to atropine was maximum against the background of noradrenergic system activation and less pronounced during stimulation of the serotoninergic system. Thus, substances that are complementary to cholinergic receptors modulated adrenergic effect on the properties of red blood cells, which, in turn, can modulate the adrenergic influences on the heart rhythm via the humoral channel of regulation. Stimulation of central neurotransmitter systems that potentiates the growth of visceral adrenergic responsiveness weakens the cholinergic modulation of the adrenergic influences, especially with respect to erythrocyte responsiveness. Hence, changes in the neurotransmitter metabolism in the body can lead to coupled modulation of reception and reactivity to adrenergic- and choline-like regulatory factors at the level of erythrocyte membranes, which can be important for regulation of heart rhythm.

Coordination of robust single cell rhythms in the Arabidopsis circadian clock via spatial waves of gene expression.

The Arabidopsis circadian clock orchestrates gene regulation across the day/night cycle. Although a multiple feedback loop circuit has been shown to generate the 24-hr rhythm, it remains unclear how robust the clock is in individual cells, or how clock timing is coordinated across the plant. Here we examine clock activity at the single cell level across Arabidopsis seedlings over several days under constant environmental conditions. Our data reveal robust single cell oscillations, albeit desynchronised. In particular, we observe two waves of clock activity; one going down, and one up the root. We also find evidence of cell-to-cell coupling of the clock, especially in the root tip. A simple model shows that cell-to-cell coupling and our measured period differences between cells can generate the observed waves. Our results reveal the spatial structure of the plant clock and suggest that unlike the centralised mammalian clock, the Arabidopsis clock has multiple coordination points.

A Conserved Circadian Function for the Neurofibromatosis 1 Gene

SUMMARYLoss of the Neurofibromatosis 1 (Nf1) protein, neurofibromin, in Drosophila disrupts circadian rhythms of locomotor activity without impairing central clock function, suggesting effects downstream of the clock. However, the relevant cellular mechanisms are not known. Leveraging the discovery of output circuits for locomotor rhythms, we dissected cellular actions of neurofibromin in recently identified substrates. Herein, we show that neurofibromin affects the levels and cycling of calcium in multiple circadian peptidergic neurons. A prominent site of action is the pars intercerebralis (PI), the fly equivalent of the hypothalamus, with cell-autonomous effects of Nf1 in PI cells that secrete DH44. Nf1 interacts genetically with peptide signaling to affect circadian behavior. We extended these studies to mammals to demonstrate that mouse astrocytes exhibit a 24-hr rhythm of calcium levels, which is also attenuated by lack of neurofibromin. These findings establish a conserved role for neurofibromin in intracellular signaling rhythms within the nervous system.

A Peptidergic Circuit Links the Circadian Clock to Locomotor Activity

The mechanisms by which clock neurons in the Drosophila brain confer an ∼24-hr rhythm onto locomotor activity are unclear, but involve the neuropeptide diuretic hormone 44 (DH44), an ortholog of corticotropin-releasing factor. Here we identified DH44 receptor 1 as the relevant receptor for rest:activity rhythms and mapped its site of action to hugin-expressing neurons in the subesophageal zone (SEZ). We traced a circuit that extends from Dh44-expressing neurons in the pars intercerebralis (PI) through hugin+ SEZ neurons to the ventral nerve cord. Hugin neuropeptide, a neuromedin U ortholog, also regulates behavioral rhythms. The DH44 PI-Hugin SEZ circuit controls circadian locomotor activity in a daily cycle but has minimal effect on feeding rhythms, suggesting that the circadian drive to feed can be separated from circadian locomotion. These findings define a linear peptidergic circuit that links the clock to motor outputs to modulate circadian control of locomotor activity.

A Cell-Autonomous Mammalian 12 hr Clock Coordinates Metabolic and Stress Rhythms

Besides circadian rhythms, oscillations cycling with a 12hr period exist. However, the prevalence, origin, regulation, and function of mammalian 12hr rhythms remain elusive. Utilizing an unbiased mathematical approach identifying all superimposed oscillations, we uncovered prevalent 12hr gene expression andmetabolic rhythms in mouse liver, coupled with a physiological 12hr unfolded protein response oscillation. The mammalian 12hr rhythm is cell autonomous, driven by a dedicated 12hr pacemaker distinct from the circadian clock, and can be entrained invitro by metabolic and ER stress cues. Mechanistically, we identified XBP1s as a transcriptional regulator of the mammalian 12hr clock. Downregulation of the 12hr gene expression strongly correlates with human hepatic steatosis and steatohepatitis, implying its importance in maintaining metabolic homeostasis. The mammalian 12hr rhythm of gene expression also is conserved in nematodes and crustaceans, indicating an ancient origin of the 12hr clock. Our work sheds new light on how perturbed biological rhythms contribute to human disease.

Effects of Lycium barbarum. polysaccharide on type 2 diabetes mellitus rats by regulating biological rhythms.

Type 2 diabetes mellitus (T2DM) is associated with circadian disruption. Our previous experimental results have showed that dietary Lycium barbarum. polysaccharide (LBP-4a) exhibited hypoglycemic and improving insulin resistance (IR) activities. This study was to explore the mechanisms of LBP-4a for improving hyperglycemia and IR by regulating biological rhythms in T2DM rats. The rats of T2DM were prepared by the high-sucrose-fat diets and injection of streptozotocin (STZ). The levels of insulin, leptin and melatonin were measured by enzyme linked immunosorbent assay (ELISA). The effect of LBP-4a on mRNA expression of melatonin receptors (MT2) in epididymal adipose tissue was evaluated by RT-PCR. The expression of CLOCK and BMAL1 in pancreatic islet cells was detected by Western blotting. Our data indicated that the 24-hr rhythm of blood glucose appeared to have consistent with normal rats after gavaged administration of LBP-4a for each day of the 4 weeks, and the effects of hypoglycemia and improving hyperinsulinemia in T2DM rats treated at high dose were much better than that at low dose. The mechanisms were related to increasing MT2 level in epididymal adipose tissue and affecting circadian clocks gene expression of CLOCK and BMAL1 in pancreatic islet cells. LBP-4a administration could treat T2DM rats. These observations provided the background for the further development of LBP-4a as a potential dietary therapeutic agent in the treatment of T2DM.

24-HOUR ACTIVITY RHYTHM AND SLEEP DISTURBANCES IN DEPRESSION AND ANXIETY: A POPULATION-BASED STUDY OF MIDDLE-AGED AND OLDER PERSONS.

Disturbed circadian rhythms have been associated with depression and anxiety, but it is unclear if disturbances in the 24-hr activity rhythm and sleep are independently and specifically related to these disorders. In 1,714 middle-aged and elderly participants of the Rotterdam Study, we collected actigraphy recordings of at least 96 hr (138 ± 14 hr, mean ± standard deviation). Activity rhythms were quantified calculating the fragmentation of the rhythm, stability of the rhythm over days, and timing of the rhythm. Total sleep time, sleep onset latency, and wake after sleep onset were also estimated with actigraphy. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression scale, persons with clinically relevant depressive symptoms were interviewed to diagnose DSM-IV-depressive disorder. Anxiety disorders were determined with the Munich version of the Composite International Diagnostic Interview. More fragmented rhythms were associated with clinically relevant depressive symptoms (odds ratio (OR): 1.27, 95% confidence interval (CI): 1.04;1.54) and anxiety disorders (OR: 1.39, 95% CI: 1.14;1.70) after covariate adjustment. Less stable rhythms, longer sleep onset latency, and more wake after sleep onset were related to clinically relevant depressive symptoms or anxiety disorders only if not adjusted for covariates and other activity rhythm and sleep indicators. Our study in middle-aged and elderly persons suggests that fragmentation of the 24-hr activity rhythm is associated with depression and anxiety. Moreover, this association also largely accounts for the effect of disturbed sleep on these psychiatric disorders.

Reduced Amplitude of the 24 Hour Activity Rhythm

In this study, we sought to advance understanding of trait vulnerability to bipolar disorder (BD) by testing whether instability of the 24-hr activity rhythm was a biomarker of the trait. Locomotor activity was measured over 7 days using actigraphy in participants allocated to groups of high ( n = 36) and low ( n = 36) trait vulnerability for BD. As predicted, the high-vulnerability group recorded a significantly lower 24-hr activity rhythm amplitude than the low-vulnerability group, indicating a less stable activity pattern. Consistent with the notion of accumulating risk, results showed the lowest activity rhythm amplitudes in participants in the high-vulnerability group with a history of depression. Secondary investigations showed that mania proneness explained more variance than depression proneness, pointing to specificity of the findings for BD. The data reinforce claims that instability of daily rhythms is a biomarker of trait vulnerability to BD.

Impact of photoperiod on circadian trehalose and trehalase rhythms in the digestive system of silkworm, Bombyx mori

Circadian trehalose and trehalase rhythms were studied in the digestive system of Bombyx mori under 12 hr light-dark cycle (LD), continuous light (LL) and continuous dark (DD). The rhythmic changes were interpreted as synthetic cycles in gut wall and release cycles in gut lumen. The trehalose rhythm of gut wall comprised 8 trehalose synthetic cycles (TS cycles) under LD and LL and 7 under DD. The 24 hr trehalose rhythm of LD and LL was clock shifted to 27.2 hr under DD. The trehalose rhythm included 4 TR cycles under LD, 5 under LL and DD in the gut lumen and the 24 hr rhythm of LD was clock shifted to 19.2 hr under LL and DD. In the gut wall trehalase rhythm maintained 8 trehalase enzyme synthetic cycles (TES cycles) under LD, 10 LL and 7 under DD and the 24 hr rhythm of LD was clock shifted to 19.2 hr under LL and 27.2 hr under DD. In the gut lumen it included 4 TER cycles under LD and DD, 5 under LL and its 24-hr rhythm was advanced to 19.2 hr. Further analysis of data showed that LD favours trehalose synthesis, while LL and DD favour trehalase synthesis.

Impact of photoperiod on circadian sucrose and sucrase rhythms in the digestive system of silkworm, Bombyx mori.

The impact of photoperiod on circadian sucrose and sucrase rhythms were analyzed in the digestive system of Bombyx mori under 12 hr light-dark cycle (LD), continuous light (LL) and continuous dark (DD). The rhythmic changes were interpreted as synthetic cycles in gut wall and release or uptake cycles in gut lumen. The gut wall comprised 6 sucrose synthetic cycles (SS cycles) under LD, LL and 5 under DD. The 24 hr rhythm of LD and LL was clock shifted to 28.8 hr under DD. In gut content, the sucrose rhythm showed 7 sucrose uptake cycles (SUcycles) under LD, 6 under LL and 5 under DD and the 24 hr rhythm of LD was clock shifted to 28.0 hr under LL and 34 hr under DD. In the gut wall sucrase rhythm maintained 7 SES cycles under LD and DD and 9 cycles under LL and its 24-hr rhythm is advanced to 18.2 hr. In the gut lumen 5 SER cycles under LD, 8 under LL and 6 under DD and its rhythm is advanced to 15 hr under LL and 20 hr under DD. Further analysis of data showed that LD favoured both synthesis and uptake of sucrose while LL, favoured the sucrase synthesis and its release.

Mechanism for 12 Hr Rhythm Generation by the Circadian Clock

In addition to the well-known circadian rhythms in animal behavior, cell biology, and gene expression, there are also 12 hr rhythms. The mechanism giving rise to these 12 hr rhythms is not clear. We worked with the hypothesis that observed 12 hr rhythms in gene expression are the results of an interplay between components of the circadian clock. Analysis of mouse liver expression data indeed revealed a strong circadian component in observed 12 hr gene expression rhythms. We show theoretically that pairs of circadian transcription factors with certain circadian phase relationships can give rise to these 12 hr rhythms, if binding noncompetitively to the promoters of regulated genes. We took an inventory of circadian transcription factors in mouse liver using available microarray data and matched these to predicted binding sites in the promoters of genes displaying 12 hr rhythms. Binding sites for transcription factor pairs with phase relationships predicted by theory were overrepresented in these promoters.

Characterization of Circadian Behavior in the Starlet Sea Anemone, Nematostella vectensis

BackgroundAlthough much is known about how circadian systems control daily cycles in the physiology and behavior of Drosophila and several vertebrate models, marine invertebrates have often been overlooked in circadian rhythms research. This study focuses on the starlet sea anemone, Nematostella vectensis, a species that has received increasing attention within the scientific community for its potential as a model research organism. The recently sequenced genome of N. vectensis makes it an especially attractive model for exploring the molecular evolution of circadian behavior. Critical behavioral data needed to correlate gene expression patterns to specific behaviors are currently lacking in N. vectensis.Methodology/Principal FindingsTo detect the presence of behavioral oscillations in N. vectensis, locomotor activity was evaluated using an automated system in an environmentally controlled chamber. Animals exposed to a 24 hr photoperiod (12 hr light: 12 hr dark) exhibited locomotor behavior that was both rhythmic and predominantly nocturnal. The activity peak occurred in the early half of the night with a 2-fold increase in locomotion. Upon transfer to constant lighting conditions (constant light or constant dark), an approximately 24 hr rhythm persisted in most animals, suggesting that the rhythm is controlled by an endogenous circadian mechanism. Fourier analysis revealed the presence of multiple peaks in some animals suggesting additional rhythmic components could be present. In particular, an approximately 12 hr oscillation was often observed. The nocturnal increase in generalized locomotion corresponded to a 24 hr oscillation in animal elongation.Conclusions/SignificanceThese data confirm the presence of a light-entrainable circadian clock in Nematostella vectensis. Additional components observed in some individuals indicate that an endogenous clock of approximately 12 hr frequency may also be present. By describing rhythmic locomotor behavior in N. vectensis, we have made important progress in developing the sea anemone as a model organism for circadian rhythm research.