The Mammalian Circadian Timekeeping System

Abstract

In most mammalian species, physiological processes undergo daily oscillations that are controlled by the circadian timekeeping system. This system consists of a master pacemaker located in brain’s suprachiasmatic nucleus (SCN) and peripheral slave oscillators in virtually all body cells. The SCN, whose phase is entrained by daily light-dark cycles, imposes overt rhythms in behaviour and physiology by a variety of neuronal, humoral, and physical outputs. While some of these SCN outputs have direct consequences for circadian behaviour, others serve as inputs to synchronize the countless circadian oscillators in peripheral cell types. Daily feeding-fasting cycles are the major Zeitgebers (timing cues) for the synchronization of oscillators in many peripheral organs. Circadian gene expression and physiology have been particularly well studied in the liver. In this organ, local circadian clocks play an important role in the coordination of food processing and xenobiotic detoxification. Although all investigated mammals contain a lightentrainable master clock in the SCN, some species display ultradian locomotor and feeding rhythm. For example, the common vole Microtus arvalis forages in bouts of 150min throughout the day. In this ultradian rodent circadian clock and clock-controlled genes are expressed rhythmically in the SCN, but at constant intermediate levels in peripheral tissues.