Circadian Timing: From Genetics to Behavior (original) (raw)
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The circadian cycle: daily rhythms from behaviour to genes
Embo Reports, 2005
The daily recurrence of activity and rest are so common as to seem trivial. However, they reflect a ubiquitous temporal programme called the circadian clock. In the absence of either anatomical clock structures or clock genes, the timing of sleep and wakefulness is disrupted. The complex nature of circadian behaviour is evident in the fact that phasing of the cycle
The search for circadian clock components in humans: new perspectives for association studies
Brazilian Journal of Medical and Biological Research, 2008
Individual circadian clocks entrain differently to environmental cycles (zeitgebers, e.g., light and darkness), earlier or later within the day, leading to different chronotypes. In human populations, the distribution of chronotypes forms a bell-shaped curve, with the extreme early and late types -larks and owls, respectively -at its ends. Human chronotype, which can be assessed by the timing of an individual's sleep-wake cycle, is partly influenced by genetic factors -known from animal experimentation. Here, we review population genetic studies which have used a questionnaire probing individual daily timing preference for associations with polymorphisms in clock genes. We discuss their inherent limitations and suggest an alternative approach combining a short questionnaire (Munich ChronoType Questionnaire, MCTQ), which assesses chronotype in a quantitative manner, with a genome-wide analysis (GWA). The advantages of these methods in comparison to assessing time-of-day preferences and single nucleotide polymorphism genotyping are discussed. In the future, global studies of chronotype using the MCTQ and GWA may also contribute to understanding the influence of seasons, latitude (e.g., different photoperiods), and climate on allele frequencies and chronotype distribution in different populations.
Circadian clocks, brain function, and development
Annals of the New York Academy of Sciences, 2013
Circadian clocks are temporal interfaces that organize biological systems and behavior to dynamic external environments. Components of the molecular clock are expressed throughout the brain and are centrally poised to play an important role in brain function. This paper focuses on key issues concerning the relationship among circadian clocks, brain function, and development, and discusses three topic areas: (1) sleep and its relationship to the circadian system; (2) systems development and psychopathology (spanning the prenatal period through late life); and (3) circadian factors and their application to neuropsychiatric disorders. We also explore circadian genetics and psychopathology and the selective pressures on the evolution of clocks. Last, a lively debate is presented on whether circadian factors are central to mood disorders. Emerging from research on circadian rhythms is a model of the interaction among genes, sleep, and the environment that converges on the circadian clock to influence susceptibility to developing psychopathology. This model may lend insight into effective treatments for mood disorders and inform development of new interventions.
Searching for Genes Underlying Behavior: Lessons from Circadian Rhythms
Science, 2008
The success of forward genetic (from phenotype to gene) approaches to uncover genes that drive the molecular mechanism of circadian clocks and control circadian behavior has been unprecedented. Links among genes, cells, neural circuits, and circadian behavior have been uncovered in the Drosophila and mammalian systems, demonstrating the feasibility of finding single genes that have major effects on behavior. Why was this approach so successful in the elucidation of circadian rhythms? This article explores the answers to this question and describes how the methods used successfully for identifying the molecular basis of circadian rhythms can be applied to other behaviors such as anxiety, addiction, and learning and memory.
Brain Research Reviews, 1993
Circadian rhythms are a ubiquitous adaptation of eukaryotic organisms to the most reliable and predictable of environmental changes, the daily cycles of light and temperature. Prominent daily rhythms in behavior, physiology, hormone levels and biochemistry &eluding gene expression) are not merely responses to these environmental cycles, however, but embody the organism's ability to keep and tell time. At the core of circadian systems is a mysterious mechanism, located in the brain (actually the suprachiasmatic nucleus of the hypothalamus) of mammals, buf present even in unicellular organisms, that functions as a clock. This clock drives circadian rhythms. It is independent of, but remains responsive to, environmental cycles (especially light). The interest in temporal regulation-its organization, mechanism and consequences-unites investigators in diverse disciplines studying otherwise disparate systems. This diversity is reflected in the brief reviews that summarize the ~~sen~a~jons at a meeting on circadian rhythms held in New York City on October 31,1992. The meeting was sponsored by the Fandation pour I'Etude du Systime Nerveux (FESN) and followed a larger meeting heId 18 manths eartier in Geneva, whose proceedings have been published (M. Katz (Ed,), Report of the Ninth FESN Study Group on 'Circadian Rhythms', Disc~&~~ in Newosc&ceJ Vd KY& Mm.
Life between Clocks: Daily Temporal Patterns of Human Chronotypes
Human behavior shows large interindividual variation in temporal organization. Extreme "larks" wake up when extreme "owls" fall asleep. These chronotypes are attributed to differences in the circadian clock, and in animals, the genetic basis of similar phenotypic differences is well established. To better understand the genetic basis of temporal organization in humans, the authors developed a questionnaire to document individual sleep times, self-reported light exposure, and self-assessed chronotype, considering work and free days separately. This report summarizes the results of 500 questionnaires completed in a pilot study. Individual sleep times show large differences between work and free days, except for extreme early types. During the workweek, late chronotypes accumulate considerable sleep debt, for which they compensate on free days by lengthening their sleep by several hours. For all chronotypes, the amount of time spent outdoors in broad daylight significantly affects the timing of sleep: Increased self-reported light exposure advances sleep. The timing of selfselected sleep is multifactorial, including genetic disposition, sleep debt accumulated on workdays, and light exposure. Thus, accurate assessment of genetic chronotypes has to incorporate all of these parameters. The dependence of human chronotype on light, that is, on the amplitude of the light:dark signal, follows the known characteristics of circadian systems in all other experimental organisms. Our results predict that the timing of sleep has changed during industrialization and that a majority of humans are sleep deprived during the workweek. The implications are far ranging concerning learning, memory, vigilance, performance, and quality of life.
On the Adaptive Significance of Circadian Clocks for Their Owners
Chronobiology International, 2013
Circadian rhythms are believed to be an evolutionary adaptation to daily environmental cycles resulting from Earth's rotation about its axis. A trait evolved through a process of natural selection is considered as adaptation; therefore, rigorous demonstration of adaptation requires evidence suggesting evolution of a trait by natural selection. Like any other adaptive trait, circadian rhythms are believed to be advantageous to living beings through some perceived function. Circadian rhythms are thought to confer advantage to their owners through scheduling of biological functions at appropriate time of daily environmental cycle (extrinsic advantage), coordination of internal physiology (intrinsic advantage), and through their role in responses to seasonal changes. So far, the adaptive value of circadian rhythms has been tested in several studies and evidence indeed suggests that they confer advantage to their owners. In this review, we have discussed the background for development of the framework currently used to test the hypothesis of adaptive significance of circadian rhythms. Critical examination of evidence reveals that there are several lacunae in our understanding of circadian rhythms as adaptation. Although it is well known that demonstrating a given trait as adaptation (or setting the necessary criteria) is not a trivial task, here we recommend some of the basic criteria and suggest the nature of evidence required to comprehensively understand circadian rhythms as adaptation. Thus, we hope to create some awareness that may benefit future studies in this direction.
Sleep, Circadian Rhythms, and Interval Timing: Evolutionary Strategies to Time Information
Frontiers in Integrative Neuroscience, 2012
A crucial property of the brain is to integrate temporal information with accurate physiological responses . Evolution has favored biological clocks that dictate homeostatic processes (e.g., the circadian timing of sleep) and, on a smaller time-scale, timed behavioral responses (e.g., interval timing). The interplay between such time-keeping mechanisms is intriguing but biologically complex. Moreover, in biology, analogous problems can be successfully solved by multiple computations. In this article I will discuss of sleep, circadian rhythms, and interval timing by delineating several aspects that suggest a common evolutionary role in providing neurobiological mechanisms for temporal information processing.
Circadian clocks - from genes to complex behaviour
Reproduction Nutrition Development, 1999
Circadian clocks control temporal structure in practically all organisms and on all levels of biology, from gene expression to complex behaviour and cognition. Over the last decades, research has begun to unravel the physiological and, more recently, molecular mechanisms that underlie this endogenous temporal programme. The generation of circadian rhythms can be explained, at the molecular level, by a model based upon a set of genes and their products which form an autoregulating negative feedback loop. The elements contributing to this transcriptional feedback appear to be conserved from insects to mammals. Here, we summarize the process of the genetic and molecular research that led to 'closing the molecular loop'. Now that the reductionist approach has led to the description of a detailed clock model at the molecular level, further insights into the circadian system can be provided by combining the extensive knowledge gained from decades of physiological research with molecular tools, thereby reconstructing the clock within the organism and its environment. We describe experiments combining old and new tools and show that they constitute a powerful approach to understanding the mechanisms that lead to temporal structure in complex behaviour. © Inra/Elsevier, Paris