ON THE NATURE OF THE CIRCADIAN CLOCK IN MAMMALS

The evidence for the essential role of the suprachiasmatic nucleus (SCN) for the generation and maintenance of circadian rhythms in mammals is briefly reviewed. The pharmacology of the phase-response curve is considered and a new circadian measure, the phase-dose-response surface (PDRS), is introduced. The role of neurotransmission, ion fluxes, and nonneuronal cellular elements in the generation and maintenance of circadian rhythmicity is considered. Cell culture of the SCN is proposed as a tool for the functional analysis of clock mechanism. The critical contribution of coupling and synchronization of clock elements is reviewed in the context of the explicit predictions generated by a strong coupling model of the circadian clock. Finally, the nature of the circadian output signal is analyzed from a phylogenetic viewpoint.