Period determination in the food-entrainable and methamphetamine-sensitive circadian oscillator(s)

• Published in: Proceedings of the National Academy of Sciences - PNAS 2012-08, Vol.109 (35), p.14218-14223
• Main Authors: Pendergast, Julie S, Oda, Gisele A, Niswender, Kevin D, Yamazaki, Shin
• Format: Article
• Language: English
• Subjects: Ad libitum feeding; Anatomy & physiology; Animals; Anticipation, Psychological - physiology; Biological clocks; Biological Sciences; Central Nervous System Stimulants - pharmacology; circadian rhythm; Circadian Rhythm - drug effects; Circadian Rhythm - physiology; Feeding Behavior - physiology; Female; Food; Food availability; Food deprivation; Food Deprivation - physiology; Gene expression; Gene loci; genes; loci; Male; Mathematical constants; Mathematical models; Mechanical oscillators; Methamphetamine; Methamphetamine - pharmacology; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Motor Activity - physiology; Oscillators; Period Circadian Proteins - genetics; Period Circadian Proteins - physiology; Photoperiod; Restricted feeding; Rodents; Suprachiasmatic Nucleus - physiology; tissues
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1206213109

Daily rhythmic processes are coordinated by circadian clocks, which are present in numerous central and peripheral tissues. In mammals, two circadian clocks, the food-entrainable oscillator (FEO) and methamphetamine-sensitive circadian oscillator (MASCO), are “black box” mysteries because their anatomical loci are unknown and their outputs are not expressed under normal physiological conditions. In the current study, the investigation of the timekeeping mechanisms of the FEO and MASCO in mice with disruption of all three paralogs of the canonical clock gene, Period, revealed unique and convergent findings. We found that both the MASCO and FEO in Per1 ⁻/⁻/Per2 ⁻/⁻/Per3 ⁻/⁻ mice are circadian oscillators with unusually short (∼21 h) periods. These data demonstrate that the canonical Period genes are involved in period determination in the FEO and MASCO, and computational modeling supports the hypothesis that the FEO and MASCO use the same timekeeping mechanism or are the same circadian oscillator. Finally, these studies identify Per1 ⁻/⁻/Per2 ⁻/⁻/Per3 ⁻/⁻ mice as a unique tool critical to the search for the elusive anatomical location(s) of the FEO and MASCO.