The suprachiasmatic nucleus and the circadian time-keeping system revisited

Many physiological and behavioral processes show circadian rhythms which are generated by an internal time-keeping system, the biological clock. In rodents, evidence from a variety of studies has shown the suprachiasmatic nucleus (SCN) to be the site of the master pacemaker controlling circadian rhythms. The clock of the SCN oscillates with a near 24-h period but is entrained to solar day/night rhythm by light. Much progress has been made recently in understanding the mechanisms of the circadian system of the SCN, its inputs for entrainment and its outputs for transfer of the rhythm to the rest of the brain. The present review summarizes these new developments concerning the properties of the SCN and the mechanisms of circadian time-keeping. First, we will summarize data concerning the anatomical and physiological organization of the SCN, including the roles of SCN neuropeptide/neurotransmitter systems, and our current knowledge of SCN input and output pathways. Second, we will discuss SCN transplantation studies and how they have contributed to knowledge of the intrinsic properties of the SCN, communication between the SCN and its targets, and age-related changes in the circadian system. Third, recent findings concerning the genes and molecules involved in the intrinsic pacemaker mechanisms of insect and mammalian clocks will be reviewed. Finally, we will discuss exciting new possibilities concerning the use of viral vector-mediated gene transfer as an approach to investigate mechanisms of circadian time-keeping.