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Extraordinary behavioral entrainment following circadian rhythm bifurcation in mice.

ABSTRACT: The mammalian circadian timing system uses light to synchronize endogenously generated rhythms with the environmental day. Entrainment to schedules that deviate significantly from 24?h (T24) has been viewed as unlikely because the circadian pacemaker appears capable only of small, incremental responses to brief light exposures. Challenging this view, we demonstrate that simple manipulations of light alone induce extreme plasticity in the circadian system of mice. Firstly, exposure to dim nocturnal illumination (<0.1 lux), rather than completely dark nights, permits expression of an altered circadian waveform wherein mice in light/dark/light/dark (LDLD) cycles "bifurcate" their rhythms into two rest and activity intervals per 24?h. Secondly, this bifurcated state enables mice to adopt stable activity rhythms under 15 or 30?h days (LDLD T15/T30), well beyond conventional limits of entrainment. Continuation of dim light is unnecessary for T15/30 behavioral entrainment following bifurcation. Finally, neither dim light alone nor a shortened night is sufficient for the extraordinary entrainment observed under bifurcation. Thus, we demonstrate in a non-pharmacological, non-genetic manipulation that the circadian system is far more flexible than previously thought. These findings challenge the current conception of entrainment and its underlying principles, and reveal new potential targets for circadian interventions.

SUBMITTER: Harrison EM

PROVIDER: S-EPMC5144065 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Extraordinary behavioral entrainment following circadian rhythm bifurcation in mice.

Harrison Elizabeth M EM Walbeek Thijs J TJ Sun Jonathan J Johnson Jeremy J Poonawala Qays Q Gorman Michael R MR

Scientific reports 20161208

The mammalian circadian timing system uses light to synchronize endogenously generated rhythms with the environmental day. Entrainment to schedules that deviate significantly from 24 h (T24) has been viewed as unlikely because the circadian pacemaker appears capable only of small, incremental responses to brief light exposures. Challenging this view, we demonstrate that simple manipulations of light alone induce extreme plasticity in the circadian system of mice. Firstly, exposure to dim nocturn ...[more]

PMID: 27929128

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Project description:The circadian rhythm, called Process C, regulates a wide range of biological processes in humans including sleep, metabolism, body temperature, and hormone secretion. Light is the dominant synchronizer of the circadian rhythm-it has been used to regulate the circadian phase to cope with jet-lag, shift work, and sleep disorder. The homeostatic oscillation of the sleep drive is called Process S. Process C and Process S together determine the sleep-wake cycle in what is known as the two-process model. This paper addresses the regulation of both Process C and Process S by scheduling light exposure and sleep based on numerical simulations of circadian rhythm and sleep mathematical models. This is a significant step beyond the existing literature that only considers the entrainment of Process C. Regulation of the two-process model poses several unique features and challenges: 1. Process S is non-smooth, i.e., the homeostatic dynamics are different in the sleep and wake regimes; 2. Light only indirectly affects Process S through Process C; 3. Light does not affect Process C during sleep. We consider two scenarios: optimizing light intensity as the control input with spontaneous (i.e., unscheduled) sleep/wake times and jointly optimizing the light intensity and the sleep/wake times, which allows limited delayed sleep and early waking as part of the decision variables. We solve the time-optimal entrainment problem for the two-process model for both scenarios using an extension of the gradient descent algorithm to non-smooth systems. To illustrate the efficacy of our time-optimal entrainment strategies, we consider two common use cases: transmeridian travelers and shift workers. For transmeridian travelers, joint optimization of the two-process model avoids the unrealistic long wake duration when only Process C is considered. The entrainment time also decreases when both the light input and the sleep schedule are optimized compared to when only the light input is optimized. For shift workers, we show that the entrainment time is significantly shortened by optimizing the night shift working light.

Project description:It is now well established that resistance exercise stimulates muscle protein synthesis and promotes gains in muscle mass and strength. However, considerable variability exists following standardized resistance training programs in the magnitude of muscle cross-sectional area and strength responses from one individual to another. Several studies have recently posited that alterations in satellite cell population, myogenic gene expression and microRNAs may contribute to individual variability in anabolic adaptation. One emerging factor that may also explain the variability in responses to resistance exercise is circadian rhythms and underlying molecular clock signals. The molecular clock is found in most cells within the body, including skeletal muscle, and principally functions to optimize the timing of specific cellular events around a 24 h cycle. Accumulating evidence investigating the skeletal muscle molecular clock indicates that exercise-induced contraction and its timing may regulate gene expression and protein synthesis responses which, over time, can influence and modulate key physiological responses such as muscle hypertrophy and increased strength. Therefore, the circadian clock may play a key role in the heterogeneous anabolic responses with resistance exercise. The central aim of this Hypothesis and Theory is to discuss and propose the potential interplay between the circadian molecular clock and established molecular mechanisms mediating muscle anabolic responses with resistance training. This article begins with a current review of the mechanisms associated with the heterogeneity in muscle anabolism with resistance training before introducing the molecular pathways regulating circadian function in skeletal muscle. Recent work showing members of the core molecular clock system can regulate myogenic and translational signaling pathways is also discussed, forming the basis for a possible role of the circadian clock in the variable anabolic responses with resistance exercise.

Project description:Study objectivesWhile light therapy has proven effective in re-entraining circadian rhythms, the potential of such an intervention has not been evaluated systematically in post-comatose patients with disorders of consciousness (DOC), who often have strongly altered circadian rhythms.MethodsWe recorded skin temperature over 7-8 days in patients with DOC in each of two conditions: habitual light (HL), and dynamic daylight (DDL) condition. While patients were in a room with usual clinic lighting in the HL condition, they were in an otherwise comparable room with biodynamic lighting (i.e. higher illuminance and dynamic changes in spectral characteristics during the day) in the DDL condition. To detect rhythmicity in the patients' temperature data, we computed Lomb-Scargle periodograms and analyzed normalized power, and peak period. Furthermore, we computed interdaily stability and intradaily variability, which provide information about rhythm entrainment and fragmentation.ResultsWe analyzed data from 17 patients with DOC (i.e. unresponsive wakefulness syndrome [n = 15] and minimally conscious state [n = 2]). The period length of the patients' temperature rhythms was closer to 24 h in the DDL as compared to the HL condition (median median deviation from 24 h: DDL = 0.52 h, HL = 3.62 h). Specifically, in 11/17 (65%) patients the period length was closer to 24 h in the DDL condition. Furthermore, the patients' rhythm was more pronounced, more stable, and less variable in the DDL condition.ConclusionsOur results indicate that DDL stimulation entrains and stabilizes circadian rhythms. This highlights the importance of adequate room lighting as an adjunct therapeutic approach for improving circadian rhythms in severely brain-injured patients.Trial registration informationGerman Clinical Trials Register (DRKS00016041); registration: 18.01.2019; recording start: 04.06.2019 https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016041.

Dataset Information

Extraordinary behavioral entrainment following circadian rhythm bifurcation in mice.

Publications

Extraordinary behavioral entrainment following circadian rhythm bifurcation in mice.

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