Dynamics of Multistage Circadian System and Applications to JetLag

Abstract

We designed a model of the circadian system based on data gathered from a number of studies of rats. The model’s parameters take into account the system’s hierarchical nature with and downstream the SCN, the electrophysiological and behavioral animal data following re-entrainment, and the differences in natural circadian times in different organs e.g. liver, lungs, etc. Our simulations of the dynamics of a multistage circadian system reveal the flexibility and stability inherent in a multistage system, as well as potential pitfalls. The modeling predicts that jet lag tends to be most severe following an eastward change of 5-8 time zones due to prolonged desynchrony of the system. This desynchrony is partly due to differing reentrainment rates among components which follow the SCN command to change their pick times, but a much greater source of desynchrony is the antidromic reentrainment of some but not all organs, where they follow the advance of the SCN in time by delaying their activity all the way around the circle to the other direction. Such antidromic reentrainment can be triggered by the overshoot of the master pacemaker's phase in response to large advances. Based on the multistage system dynamics, we design a simple protocol that results in a more orderly transition that avoids antidromic reentrainment in all components, thereby reducing the reentrainment time from nearly two weeks to just a few days for the most difficult shifts. We compare the predicted behavior of damped versus robust oscillatory components in the system, as well as the effect of weak versus strong coupling from the master pacemaker to the peripheral components.

This work has attracted some attention in the general media including Yahoo news, Science Daily, Globes, Forbes, National public radio, Good Morning New York, and many more. This is joint work with Tanya Leise.