Finding time for dinner: real-time bioluminescence reporting of circadian gene expression in food-entrained rodents

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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 is only indirectly involved in synchrony to daily mealtimes. Our research aims to understand the brain mechanisms by which daily rhythms of behaviour and physiology are synchronized to predictable daily mealtimes. 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 negative and positive feedback loops that produce self-sustaining, cell autonomous rhythmicity. Transgenic rats and mice are now available in which the firefly luciferase gene has been fused with the promotor of one of these circadian clock genes, such that brain and organ tissues emit light when the clock gene is expressed. Tissue from specific brain regions and peripheral organs can be extracted and maintained for many weeks in culture, during which bioluminescence can be measure continuously, in real time, by photometry. We will use this equipment grant to purchase a photometry system with which we will address fundamental questions about the organization of the brain system that generates food-synchronized daily rhythms. Specific objectives will be to 1. determine the location in the brain (or periphery) of the circadian clocks that control food-synchronized behavioral, autonomic and endocrine rhythms, 2. determine whether synchrony of rhythms to 2 or more daily mealtimes involves a single or a multiple clock system, and 3. determine how the timing of feeding and fasting affects the rate at which circadian rhythms reset in response to a shift of the daily light-dark cycle. This information will help us understand how the brain regulates daily rhythms, and how meal timing may be used to minimize disruption of circadian timekeeping following shifts of light-dark.