Modeling the mammalian circadian clock with transcriptional feedback loops and cAMP signaling

In this paper, we construct a new mathematical model by incorporating both transcriptional/translational feedback loops and cAMP-mediated feedback loop into the mammalian circadian oscillator. Except for reproducing typical experimental observations, the model shows that (i) for a weak TTFL, cAMP can sustain transcriptional rhythms of the mammalian circadian clock, (ii) for a strong TTFL, cAMP can only modulate the period and amplitude of transcriptional rhythms. The authors conclude that to understand the timekeeping mechanism of suprachiasmatic nucleus neurons, the transcriptional feedback loops should not be isolated from intracellular cAMP-dependent signaling.