Finding time for dinner: neural and molecular mechanisms of food-entrainable circadian clocks

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The behaviour and physiology of mammals is regulated by endogenous circadian (24 h) clocks in the brain and in peripheral organs and tissues. These clocks generate daily rhythms of sleep-wake, appetite and body temperature and coordinate the functions of all organ systems with daily cycles of light-dark and mealtimes. A master circadian clock located in the hypothalamus is critical for synchronizing daily rhythms to light-dark cycles, but synchrony to mealtimes is mediated by one or more other circadian clocks at an unknown location. Our research aims to understand the brain mechanisms by which food regulates daily rhythms. Recent advances in the molecular biology of circadian timekeeping have identified a number of genes that exhibit circadian rhythms of expression, and that form interlocking feedback loops that produce self-sustaining, cell autonomous rhythmicity. We will use immunocytochemical and photometric techniques to measure clock genes and identify brain regions that oscillate in synchrony with one or two daily mealtimes. We will explore the role of specific rhythmic brain regions in the control of meal synchronized rhythms, using lesion techniques. We will explore the role of specific clock genes for meal synchronized rhythms using clock gene mutant mice. Finally, we will characterize the effects of meal timing and food deprivation on the rate at which behavioural and physiological rhythms re-synchronize following phase shifts of the light-dark cycle, simulating east or west travel or shift work rotations. The results of these studies will clarify neural and molecular mechanisms by which food regulates daily rhythms and may suggest techniques for minimizing disruption of circadian rhythms following travel or shift rotation.