Circadian rhythms are fundamental to living organisms. The mammalian circadian system is a multi-oscillatory system composed of a master pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN) and many other oscillators located in peripheral organs. The SCN entrains to the environmental light-dark cycle and adjusts physiological and behavioral rhythms accordingly. Another putative pacemaker, the food-entrainable oscillator (FEO), entrains to feeding cycles. This oscillator is located outside of the SCN and controls food anticipatory activity. For more than 90 years the anatomical locus of the FEO has eluded scientists. However, recent studies have revealed the FEO oscillates without canonical circadian genes. We will capitalize on this discovery by performing non-biased screening for the brain area responsible for FEO timekeeping in mice without functional circadian genes. Successful completion of the proposed experiments will be a long-awaited advance; one essential to identifying the neural basis of anticipatory feeding behavior. This is necessary to understand the non-canonical molecular circadian timekeeping mechanisms and the function of the FEO. Disruption of the clock system with shiftwork and/or artificial light at night has been implicated as a risk factor for human diseases. In addition, sleep and circadian rhythms are impaired in several neurological disorders. An innovative approach to treating people with sleep and circadian related disorders is to regulate the timing of meals. Therefore, understanding the mechanistic basis of the FEO (how the rhythm is generated and synchronized to the environment) is necessary for developing strategies to treat and prevent diseases caused by circadian disruptions.
For more than 90 years, the locus of the FEO has remained elusive. Combining transgenic mice, cutting-edge bioluminescence recording, and whole-brain florescence imaging, we have assembled an innovative toolset that makes this discovery tangible. The impact of discovering the FEO locus will greatly influence our understanding of not only the molecular and physiological components of circadian rhythmicity, but also their implications on human health.
| Pendergast, Julie S; Wendroth, Robert H; Stenner, Rio C et al. (2017) mPeriod2 Brdm1 and other single Period mutant mice have normal food anticipatory activity. Sci Rep 7:15510 |
