Molecular mechanism of suppression of circadian rhythms by a critical stimulus

Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
The EMBO Journal (Impact Factor: 10.43). 12/2006; 25(22):5349-57. DOI: 10.1038/sj.emboj.7601397
Source: PubMed


Circadian singularity behavior (also called suppression of circadian rhythms) is a phenomenon characterized by the abolishment of circadian rhythmicities by a critical stimulus. Here we demonstrate that both temperature step up and light pulse, stimuli that activate the expression of the Neurospora circadian clock gene frequency (frq), can trigger singularity behavior in this organism. The arrhythmicity is transient and is followed by the resumption of rhythm in randomly distributed phases. In addition, we show that induction of FRQ expression alone can trigger singularity behavior, indicating that FRQ is a state variable of the Neurospora circadian oscillator. Furthermore, mutations of frq lead to changes in the amplitude of FRQ oscillation, which determines the sensitivity of the clock to phase-resetting cues. Our results further suggest that the singularity behavior is due to the loss of rhythm in all cells. Together, these data suggest that the singularity behavior is due to a circadian negative feedback loop driven to a steady state after the critical treatment. After the initial arrhythmicity, cell populations are then desynchronized.

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Available from: Guocun Huang, Apr 17, 2015
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    • "In 1970, Winfree reported that a specific, dim, blue-light pulse stimulus, with a unique stimulus time and duration, resulted in unusual broadening of the daily eclosion peaks of the fruit fly, Drosophila pseudoobscura, even to the extreme of obscuring circadian rhythm [10]. This phenomenon, suppression of circadian rhythms, was called ‘circadian singularity behavior’ [147], and has since been described in a range of organisms including algae, plants, and mammals [147, 148]. In humans, circadian rhythms of rectal temperature and plasma cortisol were reported to be abolished by a single, long-duration bright-light pulse administered during one or two successive circadian cycles [148]. "
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    • "Ukai et al. [52] reported that a critical light pulse (3 h light pulses delivered at an approximately specific circadian time (CT) $17 (near subjective midnight (=CT18))) drives cellular clocks into singularity behavior in mammals. Interestingly, this phenomenon is transient [113], although the removal of the stimulus is needed. The essence of asynchronization is the disturbance of various aspects (e.g., cycle, amplitude, phase and interrelationship ) of the biological rhythms that normally exhibit circadian oscillation, presumably involving decreased serotonergic system activity. "
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