Structure and function in circadian timing systems: evidence for multiple coupled circadian oscillators.

Considerable progress has been made in elucidating the mechanisms underlying the generation of circadian rhythmicity. This review describes several distinct lines of evidence which converge on the general hypothesis that circadian timing systems consist of multiple circadian oscillators, coordinated by both hierarchical and non-hierarchical coupling relationships. Such a view is supported by the complex phenomenology of circadian systems, as well as by physiological considerations. We have attempted wherever possible to integrate these two sources of evidence, in order to define the current "state of the art" in bridging the gap between structure and function in the analysis of circadian timing systems. While we concentrate mainly on the mammalian, and particularly the rodent, circadian system, we also incorporate comparative evidence obtained from a variety of vertebrate and invertebrate species.