Global parameter search reveals design principles of the mammalian circadian clock

Background Virtually all living organisms have evolved a circadian (~24 hour) clock that controls physiological and behavioural processes with exquisite precision throughout the day/night cycle. The suprachiasmatic nucleus (SCN), which generates these ~24 h rhythms in mammals, consists of several thousand neurons. Each neuron contains a gene-regulatory network generating molecular oscillations, and the individual neuron oscillations are synchronised by intercellular coupling, presumably via neurotransmitters. Although this basic mechanism is currently accepted and has been recapitulated in mathematical models, several fundamental questions about the design principles of the SCN remain little understood. For example, a remarkable property of the SCN is that the phase of the SCN rhythm resets rapidly after a 'jet lag' type experiment, i.e. when the light/dark (LD) cycle is abruptly advanced or delayed by several hours.