A Phenomenological Mouse Circadian Pacemaker Model.

ABSTRACT

Mathematical models have been used extensively in chronobiology to explore characteristics of biological clocks. In particular, for human circadian studies, the Kronauer model has been modified multiple times to describe rhythm production and responses to sensory input. This phenomenological model comprises a single set of parameters which can simulate circadian responses in humans under a variety of environmental conditions. However, corresponding models for nocturnal rodents commonly used in circadian rhythm studies are not available and may require new parameter values for different species and even strains. Moreover, due to a considerable variation in experimental data collected from mice of the same strain, within and across laboratories, a range of valid parameters is essential. This study develops a Kronauer-like model for mice by re-fitting relevant parameters to published phase response curve and period data using total least squares. Local parameter sensitivity analysis and parameter distributions determine the parameter ranges that give a near-identical model and data distribution of periods. However, the model required further parameter adjustments to match characteristics of other mouse strains, implying that the model itself detects changes in the core processes of rhythm generation and control. The model is a useful tool to understand and interpret future mouse circadian clock experiments.