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review articleCoordination of circadian timing in mammalsSteven M. Reppert & David R. WeaverDepartment of Neurobiology, University of Massachusetts Medical School, LRB-728, 364 Plantation Street, Worcester, Massachusetts 01605, USA...........................................................................................................................................................................................................................Time in the biological sense is measured by cycles that range from milliseconds to years. Circadian rhythms, which measure time
on a scale of 24 h, are generated by one of the most ubiquitous and well-studied timing systems. At the core of this timing
mechanism is an intricate molecular mechanism that ticks away in many different tissues throughout the body. However, these
independent rhythms are tamed by a master clock in the brain, which coordinates tissue-specific rhythms according to light input
it receives from the outside world.Circadian rhythms, as exemplified by the sleep/wake cycle,
are the outward manifestation of an internal timing
system. The full force of genetic, molecular and biochemical approaches, complemented by precise behavioural observations, has rapidly advanced our
knowledge of circadian timing in mammals. The focal point of
this system is a master clock, located in the suprachiasmatic nuclei
(SCN) of the anterior hypothalamus, which orchestrates the circadian programme1. Principal advances in understanding the molecular and biochemical basis of circadian timing have provided a
rapidly evolving model of the underlying clockwork. Recent
developments have also revolutionized our view of SCN input
and output mechanisms. These include the discovery of a new
visual pathway from retina to the SCN that entrains (synchronizes)
circadian rhythms to the solar day, and the elucidation of ways in
which the SCN clock ultimately generates output rhythms in
physiology and behaviour.Defining the molecular basis of circadian timing in mammals has
profound implications. In terms of fundamental brain mechanisms,
the circadian system is among the most tractable models for
providing a complete understanding of the cellular and molecular
events connecting genes to behaviour. Thorough dissection of theFigure 1 The mammalian circadian timing system is a hierarchy of dispersedoscillators. a, The master clock in the SCN is composed of numerous clock cells. TheSCN receives light information by a direct retinohypothalamic tract (RHT) to entrain theclock to the 24-h day. The entrained SCN, in turn, coordinates the timing of slaveoscillators in other brain areas (for example, cortex) and in peripheral organs (forexample, kidney and liver). b, A single SCN neuron in culture expresses robustcircadian...