scholarly journals Circadian clock neurons maintain phase control over daily behavioral activity patterns under diverse environmental conditions

2020 ◽  
Author(s):  
Clara Lorber ◽  
Ralf Stanewsky ◽  
Angélique Lamaze
Keyword(s):  
Circadian Clock ◽  
Environmental Conditions ◽  
Activity Patterns ◽  
Time Of Day ◽  
Constant Light ◽  
Behavioral Activity ◽  
Activity Increase ◽  
Temperature Cycles ◽  
Activity Peak ◽  
Deterministic Function

AbstractProper timing of rhythmic locomotor behavior is the consequence of integrating environmental conditions and internal time within the circadian clock. The 150 clock neurons in the Drosophila melanogaster brain are organized in various clusters, controlling different aspects of the daily activity rhythms. For example, during regular 12 hr light : 12 hr dark cycles at constant temperature (LD), so called Morning (M) neurons control the activity peak in the morning, while Evening (E-) neurons regulate the activity increase at the end of the day. During the remaining times of day and night, flies are inactive, giving rise to the crepuscular behavior observed in LD. Here, we investigate if the same neuronal groups also control behavioral activity under very different environmental conditions of constant light and temperature cycles (LLTC). While the morning activity is completely absent in LLTC, a single pronounced activity peak occurs at the end of the thermophase. We show that the same E-neurons operating in LD, also regulate the evening peak in LLTC. Interestingly, neuronal activity of E-neurons is inversely correlated with behavioral activity, suggesting an inhibitory action on locomotion. Surprisingly, the E-cells responsible for synchronization to temperature cycles belong to the clock neurons containing the circadian photoreceptor Cryptochrome, previously suggested to be more important for synchronization to LD. Our results therefore support a more deterministic function of the different clock neuronal subgroups, independent of specific environmental conditions.Significance statementMaster circadian clocks in the brains of mammals and fruit fly are composed of neurons expressing varying types of neuropeptides and transmitters. This diversity along with anatomical differences indicate diverse functions of different clock neurons. In Drosophila, so-called Morning (M) and Evening (E) neurons control locomotor activity at the respective time of day during normal day/night (LD) cycles. Recent reports point to a certain degree of plasticity with regard to circadian clock neuron function, depending on specific environmental conditions. Here we show that one neuronal group, the E-neurons, instead behave as if hard-wired to their output targets. Surprisingly they direct activity to occur during the evening both under LD conditions, as well as during temperature cycles in constant light.

scholarly journals The opposing Chloride Cotransporters KCC and NKCC control locomotor activity in constant light and during long days

2021 ◽  
Author(s):  
Anna Katharina Eick ◽  
Maite Ogueta ◽  
Edgar Buhl ◽  
James J. L. Hodge ◽  
Ralf Stanewsky
Keyword(s):  
Locomotor Activity ◽  
Circadian Clock ◽  
Opposite Effect ◽  
Neuronal Response ◽  
Reversal Potential ◽  
Ion Concentration ◽  
Day Length ◽  
Constant Light ◽  
Behavioral Activity ◽  
Dependent Manner

AbstractCation Chloride Cotransporters (CCC’s) regulate intracellular chloride ion concentration ([Cl−]i) within neurons, which can reverse the direction of the neuronal response to the neurotransmitter GABA. Na+ K+ Cl− (NKCC) and K+ Cl− (KCC) cotransporters transport Cl− into or out of the cell, respectively. When NKCC activity dominates, the resulting high [Cl−]i can lead to an excitatory and depolarizing response of the neuron upon GABAA receptor opening, while KCC dominance has the opposite effect. This inhibitory-to-excitatory GABA switch has been linked to seasonal adaption of circadian clock function to changing day length, and its dysregulation is associated with neurodevelopmental disorders such as epilepsy. Constant light normally disrupts circadian clock function and leads to arrhythmic behavior. Here, we demonstrate a function for KCC in regulating Drosophila locomotor activity and GABA responses in circadian clock neurons because alteration of KCC expression in circadian clock neurons elicits rhythmic behavior in constant light. We observed the same effects after downregulation of the Wnk and Fray kinases, which modulate CCC activity in a [Cl−]i-dependent manner. Patch-clamp recordings from clock neurons show that downregulation of KCC results in a more positive GABA reversal potential, while KCC overexpression has the opposite effect. Finally, KCC downregulation represses morning behavioral activity during long photoperiods, while downregulation of NKCC promotes morning activity. In summary, our results support a model in which the regulation of [Cl−]i by a KCC/NKCC/Wnk/Fray feedback loop determines the response of clock neurons to GABA, which is important for adjusting behavioral activity to constant light and long-day conditions.

Entrainment of the Circadian Clock of the Enteric Bacterium Klebsiella aerogenes by Temperature Cycles

2019 ◽  
Author(s):  
Vincent Cassone ◽  
Jiffin K. Paulose ◽  
Charles V. Cassone ◽  
Kinga B. Graniczkowska
Keyword(s):  
Circadian Clock ◽  
Klebsiella Aerogenes ◽  
Enteric Bacterium ◽  
Temperature Cycles

scholarly journals Circadian clock protein Rev-erbα regulates neuroinflammation

2019 ◽  
Vol 116 (11) ◽  
pp. 5102-5107 ◽  
Author(s):  
Percy Griffin ◽  
Julie M. Dimitry ◽  
Patrick W. Sheehan ◽  
Brian V. Lananna ◽  
Chun Guo ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Microglial Activation ◽  
Time Of Day ◽  
Resting State Functional Connectivity ◽  
Promoter Regions ◽  
Clock Component ◽  
Glial Cultures ◽  
Inflammatory Phenotype

Circadian dysfunction is a common attribute of many neurodegenerative diseases, most of which are associated with neuroinflammation. Circadian rhythm dysfunction has been associated with inflammation in the periphery, but the role of the core clock in neuroinflammation remains poorly understood. Here we demonstrate that Rev-erbα, a nuclear receptor and circadian clock component, is a mediator of microglial activation and neuroinflammation. We observed time-of-day oscillation in microglial immunoreactivity in the hippocampus, which was disrupted in Rev-erbα−/− mice. Rev-erbα deletion caused spontaneous microglial activation in the hippocampus and increased expression of proinflammatory transcripts, as well as secondary astrogliosis. Transcriptomic analysis of hippocampus from Rev-erbα−/− mice revealed a predominant inflammatory phenotype and suggested dysregulated NF-κB signaling. Primary Rev-erbα−/− microglia exhibited proinflammatory phenotypes and increased basal NF-κB activation. Chromatin immunoprecipitation revealed that Rev-erbα physically interacts with the promoter regions of several NF-κB–related genes in primary microglia. Loss of Rev-erbα in primary astrocytes had no effect on basal activation but did potentiate the inflammatory response to lipopolysaccharide (LPS). In vivo, Rev-erbα−/− mice exhibited enhanced hippocampal neuroinflammatory responses to peripheral LPS injection, while pharmacologic activation of Rev-erbs with the small molecule agonist SR9009 suppressed LPS-induced hippocampal neuroinflammation. Rev-erbα deletion influenced neuronal health, as conditioned media from Rev-erbα–deficient primary glial cultures exacerbated oxidative damage in cultured neurons. Rev-erbα−/− mice also exhibited significantly altered cortical resting-state functional connectivity, similar to that observed in neurodegenerative models. Our results reveal Rev-erbα as a pharmacologically accessible link between the circadian clock and neuroinflammation.

scholarly journals The Application of Visual Environmental Economics in the Study of Public Preference and Urban Greenspace

2009 ◽  
Vol 36 (2) ◽  
pp. 355-375 ◽  
Author(s):  
Richard Laing ◽  
Anne-Marie Davies ◽  
David Miller ◽  
Anna Conniff ◽  
Stephen Scott ◽  
...  
Keyword(s):  
Environmental Economic ◽  
Environmental Economics ◽  
Environmental Conditions ◽  
Three Dimensional ◽  
Computer Models ◽  
Time Of Day ◽  
Public Preference ◽  
Daily Lives ◽  
Urban Greenspace ◽  
Physical Variables

Urban greenspace has consistently been argued to be of great importance to the wellbeing, health, and daily lives of residents and users. This paper reports results from a study that combined the visualisation of public results from a study that combined the visualisation of public greenspace with environmental economics, and that aimed to develop a method by which realistic computer models of sites could be used within preference studies. As part of a methodology that employed contingent rating to establish the values placed on specific greenspace sites, three-dimensional computer models were used to produce visualisations of particular environmental conditions. Of particular importance to the study was the influence of variables including lighting, season, time of day, and weather on the perception of respondents. This study followed previous work that established a suitable approach to the modelling and testing of entirely moveable physical variables within the built environment. As such, the study has established firmly that computer-generated visualisations are appropriate for use within environmental economic surveys, and that there is potential for a holistic range of attributes to be included in such studies.

scholarly journals A54 THE CIRCADIAN CLOCK INFLUENCES JAK/STAT SIGNALING AND GUT PERMEABILITY

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 11-12
Author(s):  
K Parasram ◽  
D Bachetti ◽  
P Karpowicz
Keyword(s):  
Circadian Clock ◽  
Clock Cycle ◽  
Intestinal Barrier ◽  
Fruit Fly ◽  
Cell Types ◽  
Time Of Day ◽  
Acute Injury ◽  
Intestinal Barrier Function ◽  
Intestinal Immunity ◽  
Stat Signaling

Abstract Background The circadian clock is a 24-hour feedback loop that drives rhythms in behaviours and physiological processes. This molecular timekeeper consists of the transcription factors, Clock-Cycle, that drive expression of thousands of clock-controlled genes, with two of these, Period and Timeless, acting as negative regulators of Clock-Cycle. This fundamental mechanism was initially characterized in the fruit fly, Drosophila melanogaster (Nobel Prize in Physiology & Medicine, 2017), and is highly conserved in humans. The intestine, or midgut, of Drosophila, is also similar to the human small intestine consisting of similar cellular lineage, signaling pathways, and physiological functions. The lineage of the Drosophila intestine contains the same four cell types as humans: intestinal stem cells (ISCs), progenitors called enteroblasts, enterocytes and enteroendocrine cells. This simplified lineage as well as the genetic tools available, make Drosophila an ideal model for intestinal regeneration in health and disease. We have previously shown that the circadian clock is active in ISCs, EBs and ECs during both homeostatic and regenerating conditions. Furthermore, the circadian clock regulates the mitosis of ISCs under regenerating conditions. Aims We sought to uncover if Jak/STAT signaling, one of the key pathways involved in ISC proliferation in the Drosophila intestine, shows a circadian rhythm and if there is a time-of-day difference in the regenerative response. Methods To test whether the clock regulates Jak/STAT during acute injury, we developed an irradiation assay that does not affect survival but acutely disrupts intestinal barrier function. Results Using a dynamic reporter of Jak/STAT activity we show that Period circadian clock mutants have low Jak/STAT signaling and a leaky gut phenotype. Wildtype controls show time-dependent gut leakiness upon irradiation, which is higher and time-independent in Period mutants. The level of Jak/STAT response differs depending on the time of irradiation in the controls, but is higher at all times in the mutants. Conclusions The Jak/Stat pathway regulates intestinal immunity and epithelial cell proliferation in humans, thus playing a role in colorectal cancer and inflammatory bowel disease. Our results suggest Jak/Stat is controlled by the circadian clock, which has implications for intestinal recovery following medical treatments, including radiation therapy. Funding Agencies NRC

Circadian Timekeeping in Anticancer Therapeutics: An Emerging Vista of Chronopharmacology Research

2021 ◽  
Vol 22 ◽  
Author(s):  
Alekhya Puppala ◽  
Sourbh Rankawat ◽  
Sandipan Ray
Keyword(s):  
Drug Metabolism ◽  
Circadian Clock ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Cancer Biology ◽  
Anticancer Therapy ◽  
Time Of Day ◽  
Circadian Regulation ◽  
Cancer Management ◽  
Anticancer Therapeutics

Background: Intrinsic rhythms in host and cancer cells play an imperative role in tumorigenesis and anticancer therapy. Circadian medicine in cancer is principally reliant on the control of growth and development of cancer cells or tissues by targeting the molecular clock and implementing time-of-day-based anticancer treatments for therapeutic improvements. In recent years, based on extensive high-throughput studies, we witnessed the arrival of several drugs and drug-like compounds that can modulate circadian timekeeping for therapeutic gain in cancer management. Objective: This perspective article intends to illustrate the current trends in circadian medicine in cancer, focusing on clock-modulating pharmacological compounds and circadian regulation of anticancer drug metabolism and efficacy. Scope and Approach: Considering the critical roles of the circadian clock in metabolism, cell signaling, and apoptosis, chronopharmacology research is exceedingly enlightening for understanding cancer biology and improving anticancer therapeutics. In addition to reviewing the relevant literature, we investigated the rhythmic expression of molecular targets for many anticancer drugs frequently used to treat different cancer types. Key Findings and Conclusion: There are adequate empirical pieces of evidence supporting circadian regulation of drug metabolism, transport, and detoxification. Administration of anticancer drugs at specific dosing times can improve their effectiveness and reduce the toxic effects. Moreover, pharmacological modulators of the circadian clock could be used for targeted anticancer therapeutics such as boosting circadian rhythms in the host can markedly reduce the growth and viability of tumors. All in all, precision chronomedicine can offer multiple advantages over conventional anticancer therapy.

Time-of-Day Dependent Neuronal Injury After Ischemic Stroke: Implication of Circadian Clock Transcriptional Factor Bmal1 and Survival Kinase AKT

2017 ◽  
Vol 55 (3) ◽  
pp. 2565-2576 ◽  
Author(s):  
Mustafa Caglar Beker ◽  
Berrak Caglayan ◽  
Esra Yalcin ◽  
Ahmet Burak Caglayan ◽  
Seyma Turkseven ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Circadian Clock ◽  
Neuronal Injury ◽  
Time Of Day ◽  
Transcriptional Factor

scholarly journals Eye shape and the nocturnal bottleneck of mammals

2012 ◽  
Vol 279 (1749) ◽  
pp. 4962-4968 ◽  
Author(s):  
Margaret I. Hall ◽  
Jason M. Kamilar ◽  
E. Christopher Kirk
Keyword(s):  
Visual Acuity ◽  
Detailed Analysis ◽  
Statistical Methods ◽  
Activity Pattern ◽  
Activity Patterns ◽  
Time Of Day ◽  
Visual Sensitivity ◽  
Early Evolution ◽  
Eye Size ◽  
Diurnal Species

Most vertebrate groups exhibit eye shapes that vary predictably with activity pattern. Nocturnal vertebrates typically have large corneas relative to eye size as an adaptation for increased visual sensitivity. Conversely, diurnal vertebrates generally demonstrate smaller corneas relative to eye size as an adaptation for increased visual acuity. By contrast, several studies have concluded that many mammals exhibit typical nocturnal eye shapes, regardless of activity pattern. However, a recent study has argued that new statistical methods allow eye shape to accurately predict activity patterns of mammals, including cathemeral species (animals that are equally likely to be awake and active at any time of day or night). Here, we conduct a detailed analysis of eye shape and activity pattern in mammals, using a broad comparative sample of 266 species. We find that the eye shapes of cathemeral mammals completely overlap with nocturnal and diurnal species. Additionally, most diurnal and cathemeral mammals have eye shapes that are most similar to those of nocturnal birds and lizards. The only mammalian clade that diverges from this pattern is anthropoids, which have convergently evolved eye shapes similar to those of diurnal birds and lizards. Our results provide additional evidence for a nocturnal ‘bottleneck’ in the early evolution of crown mammals.

Seasonal and daily activity patterns in a Canadian population of the prairie rattlesnake, Crotalus viridus viridis

1985 ◽  
Vol 63 (1) ◽  
pp. 86-91 ◽  
Author(s):  
V. P. J. Gannon ◽  
D. M. Secoy
Keyword(s):  
Daily Activity ◽  
Activity Patterns ◽  
High Energy ◽  
Time Of Day ◽  
Energy Demands ◽  
Level Of Activity ◽  
Canadian Population ◽  
Significant Difference ◽  
Gravid Females ◽  
Daily Activity Patterns

The seasonal and daily activity patterns of a Saskatchewan population of Crotalus viridus viridis is presented. Snakes emerged from hibernation in late April and migrated into the surrounding river valley and upland regions in early May. Adult migration preceded that of immature age-classes. Several gravid females occupied a rookery near the hibernaculum during the summer months and remained there until parturition. Females did not occupy this site in successive years and may have a biennial or greater reproductive cycle. Snakes returned to the hibernaculum in early September and remained active until early October. The behaviour of snakes in a field enclosure in response to time of day and body temperature (Tb) was recorded during the spring, summer, and fall. Significant differences in the Tb values of sunning, movement, and shading behaviours were noted. Gravid females were significantly more active in all seasons. However, no significant difference in mean Tb was found between males and females in the field, enclosure study, or laboratory thermal gradient. The observed greater level of activity may reflect the high energy demands of gravid females.

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