Sleep Modelling across Physiological Levels.

Sleep and circadian rhythms are regulated across multiple functional, spatial and temporal levels: from genes to networks of coupled neurons and glial cells, to large scale brain dynamics and behaviour. The dynamics at each of these levels are complex and the interaction between the levels is even more so, so research have mostly focused on interactions within the levels to understand the underlying mechanisms-the so-called reductionist approach. Mathematical models were developed to test theories of sleep regulation and guide new experiments at each of these levels and have become an integral part of the field. The advantage of modelling, however, is that it allows us to simulate and test the dynamics of complex biological systems and thus provides a tool to investigate the connections between the different levels and study the system as a whole. In this paper I review key models of sleep developed at different physiological levels and discuss the potential for an integrated systems biology approach for sleep regulation across these levels. I also highlight the necessity of building mechanistic connections between models of sleep and circadian rhythms across these levels.