Intended for healthcare professionals

Clinical Review

The brain, circadian rhythms, and clock genes

BMJ 1998; 317 doi: (Published 19 December 1998) Cite this as: BMJ 1998;317:1704
  1. Michael Hastings, reader in neuroscience
  1. Department of Anatomy, University of Cambridge, Cambridge CB2 3DY

    Every day we experience profound changes in our mental and physical condition as body and brain alternate between states of high activity during the waking day and recuperation, rest, and repair during night time sleep. These cycles are not a passive response to the world around us: they are pre-adapted, driven by an internal clock. We know this because when human volunteers are held in experimental isolation and deprived of any temporal or social cues, they still show daily cycles of sleep and wakefulness, in core body temperatures, and urinary output (fig 1). 12 As with all biological processes, the clock driving these cycles is slightly imperfect, therefore the measurable rhythms free run with periods of slightly less than or greater than one solar day, hence circadian (approximately a day). Notwithstanding this inaccuracy, the circadian clock is extremely robust. It is capable of continuing for several months and with a reproducibility to within a few minutes per cycle.

    Summary points

    Circadian timekeeping is a fundamental property of all higher forms of life

    In mammals the principal circadian mechanism lies in the individual neurones of the suprachiasmatic nuclei

    Comparative studies of the clock in mammals and fruit flies have provided a model of autoregulatory feedback to explain its basic properties

    The genes encoding this feedback loop, and how they and their protein products respond to synchronising cues, are being characterised

    This opens the way for an understanding of how genes regulate a basic aspect of behaviour and what are suitable targets for intervention when this timing mechanism breaks down

    FIG 1

    Most aspects of physiology and behaviour are governed by a central clock mechanism in the hypothalamus. The clock acts on neural and endocrine pathways to regulate individual circadian rhythms so that internal state varies predictably over 24 hours. This enables adaption to …

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