Light-induced Synchronization of the SCN Coupled Oscillators and Implications for Entraining the HPA Axis

The suprachiasmatic nucleus (SCN) synchronizes the physiological rhythms to the external light-dark cycle and tunes the dynamics of circadian rhythms to photoperiod fluctuations. Changes in the neuronal network topologies are suggested to cause adaptation of the SCN in different photoperiods, resulting in the broader phase distribution of neuron activities in long photoperiods (LP) compared to short photoperiods (SP). Regulated by the SCN output, the level of glucocorticoids is elevated in short photoperiod, which is associated with peak disease incidence. The underlying coupling mechanisms of the SCN and the interplay between the SCN and the HPA axis have yet to be fully elucidated. In this work, we propose a mathematical model including a multiple-cellular SCN compartment and the HPA axis to investigate the properties of the circadian timing system under photoperiod changes. Our model predicts that the probability-dependent network is more energy-efficient than the distance-dependent network. Coupling the SCN network by intra-subpopulation and inter-subpopulation forces, we identified the negative correlation between robustness and plasticity of the oscillatory network. The HPA rhythms were predicted to be strongly entrained to the SCN rhythms with a pro-inflammatory high-amplitude glucocorticoid profile under SP. The fast temporal topology switch of the SCN network was predicted to enhance synchronization when the synchronization is not complete. These synchronization and circadian dynamics alterations might govern the seasonal variation of disease incidence and its symptom severity.