Biomathematics Seminar Series - Adam Stinchcombe

Speaker: Adam Stinchcombe, University of Toronto

Title: Modelling Insights into Two Behaviour Rhythm Phenomena

Abstract: 

1. Ultradian behavioural rhythms are highly-flexible oscillations in goal-directed behaviour with periods shorter than a day. They remain mysterious in both their biochemical mechanisms and their functional significance, but are generally believed to be a reflection of neural dynamics. We propose that D2 autoreceptor-dependent dopamine self-regulation in the midbrain-striatal synapses gives rise to ultradian rhythmicity. We express this hypothesis in an ordinary differential equation based mathematical model in a dual-negative feedback-loop structure. Numerical integration and bifurcation analysis shows that the oscillations have a flexible and parameter-sensitive period in agreement with experimental observation.  The model also demonstrates the masking-entraining effects of circadian (approximately 24 hour) regulation on ultradian rhythms and the rapid-resetting effect of transient excitation. This reveals the crucial role of circadian-ultradian interaction in consolidating behavioural activity and coordinating the motivation to engage in recurring, albeit not highly predictable events, such as social interactions.

2. Many species have robust daily activity rhythms that can be driven by the timing of food intake. The cellular or molecular foundation of these oscillators have yet to be determined. Nonetheless, many interesting phenomena related to food anticipatory activity have been observed. Our experiments show that rats with running wheels can anticipate at least four daily feeding opportunities at fixed times of day and that anticipation persists at each mealtime during several circadian cycles of food deprivation in constant dark. These anticipatory behaviours also occur in rats with an ablated suprachiasmatic nucleus, the site of the central circadian pacemaker. We also observe rats anticipating two daily meals recurring with 24h and 26h periodicities that also persists during constant darkness food deprivation. We capture all of these dynamic phenomena with a mathematical model. This model consists of two groups of Kuramoto oscillators, representing the suprachiasmatic nucleus and the food entrainable oscillators. The two populations are intra- and inter-coupled and receive adapted photic input. We hypothesize that the period heterogeneity of the food entrainable oscillators is primarily responsible for the food anticipatory activity. We analyze this model using numerical simulations and the Ott-Antonson ansatz in a continuum limit. The model provides a framework to analyze previous experiments and design future experiments.

For a list of upcoming Biomathematics Seminars please visit the following website https://mathstat.uoguelph.ca/node/414