A Multiscale Model Explains the Circadian Phase Dependent Firing Pattern Variations in Suprachiasmatic Nuclei and the Occurrence of Stochastic Resonance

摘要

We perform multiscale model simulations to study the role of slow varying mammalian circadian oscillations (in hrs) and Gaussian noise in modulating the rapidly varying firing patterns (in ms) exhibited by the ionic channels of suprachiasmatic nuclei under DD (constant darkness) conditions. Hodgkin-Huxley model near subcritical Hopf bifurcation exhibits noise-induced firing patterns and these patterns, modulated by slow varying circadian gene regulatory network, are highly circadian phase dependent. The simulated firing patterns are also very close to the experimentally observed patterns with a firing rate of 3-10 HZ during subjective day and 0-3 HZ during subjective night. Further, for certain noise intensity, the model's response is maximal, a characteristic feature of stochastic resonance, but surprisingly, we observe it only at certain circadian phases. This is the first instance where it is shown that the slow-varying gene regulatory circadian oscillation along with noise modulates the firing patterns of fast varying voltage gated channel as observed in experiments and exhibits stochastic resonance only in certain circadian phases.