Suprachiasmatic Nucleus Clock Time in the Mammalian Circadian System

The integration of time from gene to system levels is an exciting feature of circadian biology. In mammals, clock cells in the suprachiasmatic nucleus (SCN) generate time by an autoregulatory transcription-(post)translational feedback loop. Clock activity in the SCN neurons is expressed as activity-dependent electric signals, which are coupled to those of other SCN neurons. The SCN spreads the time signals in a form of synchronized nerve impulses to central parasympathetic nuclei (e.g., dorsal motor nucleus of the vagus) and central sympathetic nuclei (e.g., intermediolateral cell column of the spinal cord). The vagal nerve innervates gastrointestinal and respiratory organs. Sympathetic signals to the adrenal gland are converted to hormonal (glucocorticoid) signals. Glucocorticoids released into the bloodstream bind to glucocorticoid receptors of peripheral organs, activate the mammalian Per1 gene in systemic cells, and reset the time of body clocks. Thus, the SCN-evoked time generated by specific genes localized to the SCN is converted to neuronal and hormonal signals and synchronizes the clocks in the whole body.