Internal organization of the circadian timing system in multicellular animals.

Three models of the organization of the circadian timing system in multicellular animals are presented. Each can account for the observed internal synchronization of the various circadian rhythms within the organism and each is also compatible with the known responses of circadian systems to manipulations of environmental time cues. One is a single oscillatory system (Model I) while the other two are multioscillator systems arranged in a hierarchical (Model II) or nonhierarchical (Model III) manner. Experiments that test the predictions of the different models are reviewed. These indicate that the circadian timing system in mammals is organized as a multioscillator system with oscillating concentrations of chemical mediators (nervous or endocrine) internally synchronizing the various potentially-independent oscillators by an entrainment mechanism. However, as yet there is insufficient evidence to indicate whether the oscillators are arranged with a predominantly hierarchical (Model II) or nonhierarchical (Model III) organization.