Transcription-Based Oscillator Model for Light-Induced Splitting as Antiphase Circadian Gene Expression in the Suprachiasmatic Nuclei

Abstract

Daily locomotor patterns of a variety of organisms have been interpreted as driven by dual circadian oscillators. Yet, in mammals, cellular data have revealed many circadian oscillators in the bilateral suprachiasmatic nucleus (SCN). To test how large numbers of oscillators could respond to environmental cues as a pair of oscillators, the authors developed a computational model composed of 2 groups of oscillators with strong local interactions and with weaker coupling between the 2 groups. Unlike previous models that assumed that light affects the timing or polarity of coupling between a pair of oscillators, this simulation assumed that light increased the transcription rate of a clock gene and consequently altered circadian properties of individual cells. In constant dark, weak local (within each of the 2 groups) and distant (between group) coupling established in-phase oscillations and a typical single bout of daily activity. In constant light, local synchrony developed only if coupling was strong and resulted in antiphase synchrony between the 2 groups and bimodal daily activity reminiscent of split behavior. These numerical simulations thus showed that splitting behavior can develop with increased light intensity without structural changes in the coupling topology or sign. Instead, the authors propose that light changes intrinsic oscillator properties through the increase of maximal transcription rate of a clock gene, so that as light intensity increases, the output of the coupled network transitions from a single bout of activity through irregular beating to 2 bouts and, in bright constant light, arrhythmicity.