Abstract
The mammalian circadian system is a hierarchical network of oscillators organized to optimally coordinate behavior and physiology with daily environmental cycles. The suprachiasmatic nucleus (SCN) of the hypothalamus is at the top of this hierarchy, synchronizing to the environmental light-dark cycle, and coordinates the phases of peripheral clocks. The Period genes are critical components of the molecular timekeeping mechanism of these clocks. Circadian clocks are disabled in Period1/2/3 triple mutant mice, resulting in arrhythmic behavior in constant conditions. We uncovered rhythmic behavior in this mutant by simply exposing the mice to timed access to a palatable meal or running wheel. The emergent circadian behavior rhythms free-ran for many cycles under constant conditions without cyclic environmental cues. Together, these data demonstrate that the palatable meal-inducible circadian oscillator (PICO) and wheel-inducible circadian oscillator (WICO) are generated by non-canonical circadian clocks. Entrainment of these novel oscillators by palatable snacks and timed exercise could become novel therapeutics for human conditions caused by disruptions of the circadian clocks.
Highlights
The mammalian circadian system is a hierarchical network of oscillators organized to optimally coordinate behavior and physiology with daily environmental cycles
We first used a training protocol that combined restricted feeding of both chow and a palatable meal to establish palatable meal anticipatory activity (PAA) in wild-type mice in the light-dark cycle
We tested whether PAA persisted in constant conditions by removing the daily palatable meal
Summary
The mammalian circadian system is a hierarchical network of oscillators organized to optimally coordinate behavior and physiology with daily environmental cycles. The emergent circadian behavior rhythms free-ran for many cycles under constant conditions without cyclic environmental cues Together, these data demonstrate that the palatable meal-inducible circadian oscillator (PICO) and wheel-inducible circadian oscillator (WICO) are generated by non-canonical circadian clocks. PERIOD and CRYPTOCHROME, in turn, form a complex with other proteins and negatively regulate their own transcription[6] This molecular circadian feedback loop is universal among all known clocks in the brain and peripheral tissues[7]. It is well demonstrated that restricted feeding entrains clocks in peripheral tissues[11,12,13]; a recent study suggests that this may be a mechanism independent from the appearance of FAA14 This food anticipatory activity (the output of the FEO) observed during restricted feeding immediately disappears when the animal is released to ad libitum feeding, but re-appears when the animal is subsequently food-deprived. We sought to develop an approach to expose the free-running rhythm of the FEO by www.nature.com/scientificreports/
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
