Multiple entrained oscillator model of food anticipatory circadian rhythms.

For many animal species, knowing when to look for food may be as important as knowing where to look. Rats and other species use a feeding-responsive circadian timing mechanism to anticipate, behaviorally and physiologically, a predictable daily feeding opportunity. How this mechanism for anticipating a daily meal accommodates more than one predictable mealtime is unclear. Rats were trained to press a lever for food, and then limited to one or more daily meals at fixed or systematically varying times of day. The rats were able to anticipate up to 4 of 4 daily meals at fixed times of day and two 'daily' meals recurring at 24 h and 26 h intervals. When deprived of food, in constant dark, lever pressing recurred for multiple cycles at expected mealtimes, consistent with the periodicity of the prior feeding schedule. Anticipation did not require the suprachiasmatic nucleus circadian pacemaker. The anticipation rhythms could be simulated using a Kuramoto model in which clusters of coupled oscillators entrain to specific mealtimes based on initial phase and intrinsic circadian periodicity. A flexibly coupled system of food-entrainable circadian oscillators endows rats with adaptive plasticity in daily programming of foraging activity.

A Phenomenological Mouse Circadian Pacemaker Model.

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.