ABSTRACT
This chapter highlights mechanistic studies of circadian timekeeping in mammals at the cellular and molecular level. One strategy for identifying elements of the circadian system is to trace the cascade of events that comprise the pacemaker’s entrainment pathways; ultimately these pathways must converge and terminate on components of the oscillatory machinery in order to cause phase shifts of overt rhythmicity. The cellular and molecular basis of the actual oscillatory mechanism of the circadian pacemaker in the suprachiasmatic nucleus (SCN) is unknown. Whether circadian rhythmicity is a property of individual cells or instead emerges from an intercellular interaction was the focus of much debate. Accumulating evidence that SCN cells continue to oscillate after dissociation and culture was elegantly verified using a system that simultaneously monitors the neuronal firing rates of multiple individual dispersed cells cultured on fixed microelectrode arrays. Ideas about the intracellular circadian oscillatory mechanism come mainly from initial molecular genetic studies of single-gene mutants in fruit flies and fungi.
