Synchronization and maintenance of circadian timing in the mammalian clockwork.

The hypothalamic suprachiasmatic nucleus (SCN) is the principal circadian pacemaker in mammals. Cells in the SCN contain cell-autonomous transcriptional-translational feedback loops, which are synchronised to each other and thereby provide a coherent output to direct synchrony of peripheral clocks located in the brain and body. A major difference between these peripheral clocks and the SCN is the requirement for intercellular coupling mechanisms, which confer robustness, stability and amplitude to the system. There has been remarkable progress to our understanding of the intra- and inter-cellular mechanisms of the SCN circuitry over the last ~20 years, which has come hand-in-hand with the development of new technologies to measure and manipulate the clock.