Mathematical insights into the role of dopamine signaling in circadian entrainment (Q6156875)

The authors consider a model consisting of 8 ODEs describing clock gene and protein interactions in a single suprachiasmatic nucleus cell. This system has been studied previously as a model of circadian rhythms. The model describes the effects of the circadian clock on dopamine, but the authors are interested in the reciprocal effect of dopamine on the circadian clock. They investigate the effects of varying several parameters which model changing D1 dopamine receptor (DRD1) signalling. Through numerical simulations, the response of the network to a sudden phase advance or phase delay of the external periodic light/dark drive is determined, focusing on the time needed for the system to become re-entrained to the light/dark cycle. Their findings support the idea that DRD1 signaling sets the gain on light as opposed to influencing Per transcription independently. They also model the effect of administering a REV-ERB agonist and find that administering this at the time of phase shift creates a temporary phase delay that aids in re-entrainment to the shifted light/dark schedule. The authors also investigate the effects of varying the daylight duration and find that the time courses of several genes are largely unaffected by this variation.