Abstract

The circadian clock plays a pivotal role in modulating physiological processes and has been implicated, either directly or indirectly, in a range of pathological states including cancer. Here we investigate how the circadian clock is entrained by external cues such as light. Working with zebrafish cell lines and combining light pulse experiments with simulation efforts focused on the role of synchronization effects, we find that even very modest doses of light exposure are sufficient to trigger some entrainment, whereby a higher light intensity or duration correlates with strength of the circadian signal. Moreover, we observe in the simulations that stochastic effects may be considered an essential feature of the circadian clock in order to explain the circadian signal decay in prolonged darkness, as well as light initiated resynchronization as a strong component of entrainment.

Highlights

  • In evolution’s continuous battle for the survival of the fittest, the ability to anticipate recurring environmental fluctuations has emerged as a powerful tool and immense selective advantage, allowing organisms to tailor their behaviour and biological processes to expected future opportunities and challenges

  • The importance of time keeping is often considered on a behavioural level, for example, looking to the way different higher organisms would structure their daily or seasonal behaviour in line with an inner “sense of time”: flowers synching their blooming periods to day light or, more rarely, night time hours, nocturnal rodents sensing when to return to the safety of their burrows in time before dawn, or migratory birds punctually embarking on their yearly journeys across the globe

  • Many of us are very familiar with the experience of waking up just a few minutes before the alarm clock, or having a good sense of when our usual meal times come around. It is on this level that researches started looking at the circadian clock intently from a therapeutic angle, for example, in the context of chronic sleeping disorders, or the jet lag evoked by modern means of travel

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Summary

Introduction

In evolution’s continuous battle for the survival of the fittest, the ability to anticipate recurring environmental fluctuations has emerged as a powerful tool and immense selective advantage, allowing organisms to tailor their behaviour and biological processes to expected future opportunities and challenges. It may not be surprising that most living entities, from human [1] beings to cyanobacteria [2], make use of daily time-keeping mechanisms, known as circadian clocks. These systems, are generally much more multifaceted than simple hour clocks, featuring, for example, the ability to adjust to different day light spans (photoperiods) and in doing so can even double as a useful seasonal timer. Intercontinental flights that may expose us to radically opposed time zones in a matter of hours have demonstrated to us only too well the general flexibility, and significant delay, with which our circadian rhythm adjusts to such radical perturbations

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