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

Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235-1634, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 08/2012; 109(35):14218-23. DOI: 10.1073/pnas.1206213109
Source: PubMed


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.

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    • "Similar lesion studies have not been conducted on the dorsal striatum, where damage can be expected to impair locomotor output. Finally, chronic treatment with methamphetamine and other dopaminergic psychostimulant drugs can induce a circadian activity rhythm in otherwise arrhythmic, SCN-ablated rats and mice [18,26-30]. Methamphetamine-induced rhythmicity, like food restriction schedules, is associated with induction or shifting of circadian clock gene rhythms in the striatum but not the SCN [29]. "
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    ABSTRACT: Circadian activity rhythms are jointly controlled by a master pacemaker in the hypothalamic suprachiasmatic nuclei (SCN) and by food-entrainable circadian oscillators (FEOs) located elsewhere. The SCN mediates synchrony to daily light-dark cycles, whereas FEOs generate activity rhythms synchronized with regular daily mealtimes. The location of FEOs generating food anticipation rhythms, and the pathways that entrain these FEOs, remain to be clarified. To gain insight into entrainment pathways, we developed a protocol for measuring phase shifts of anticipatory activity rhythms in response to pharmacological probes. We used this protocol to examine a role for dopamine signaling in the timing of circadian food anticipation. To generate a stable food anticipation rhythm, rats were fed 3h/day beginning 6-h after lights-on or in constant light for at least 3 weeks. Rats then received the D2 agonist quinpirole (1 mg/kg IP) alone or after pretreatment with the dopamine synthesis inhibitor α-methylparatyrosine (AMPT). By comparison with vehicle injections, quinpirole administered 1-h before lights-off (19h before mealtime) induced a phase delay of activity onset prior to the next meal. Delay shifts were larger in rats pretreated with AMPT, and smaller following quinpirole administered 4-h after lights-on. A significant shift was not observed in response to the D1 agonist SKF81297. These results provide evidence that signaling at D2 receptors is involved in phase control of FEOs responsible for circadian food anticipatory rhythms in rats.
    PLoS ONE 11/2013; 8(11):e82381. DOI:10.1371/journal.pone.0082381 · 3.23 Impact Factor
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    • "Recently, Mieda and Sakurai (2011) reported that FAA emergence is delayed and persistence attenuated in conditional knockout Bmal1 mice that lack Bmal1 specifically in the CNS. Pendergast et al. (2012) reported that in Per1/Per2/Per3 knockout mice, FAA is unstable and imprecise in a 24 h feeding schedule; yet, the animals are able to anticipate food. Interestingly, in addition to the 24 h rhythm, they exhibit a second period of ≈21 h. "
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    ABSTRACT: Mammals exhibit daily anticipatory activity to cycles of food availability. Studies on such food anticipatory activity (FAA) have been conducted mainly in nocturnal rodents. They have identified FAA as the behavioral output of a food entrained oscillator (FEO), separate of the known light entrained oscillator (LEO) located in the suprachiasmatic nucleus (SCN) of hypothalamus. Here we briefly review the main characteristics of FAA. Also, we present results on four topics of food anticipation: (1) possible input signals to FEO, (2) FEO substrate, (3) the importance of canonical clock genes for FAA, and (4) potential practical applications of scheduled feeding. This mini review is intended to introduce the subject of food entrainment to those unfamiliar with it but also present them with relevant new findings on the issue.
    Frontiers in Behavioral Neuroscience 11/2012; 6:83. DOI:10.3389/fnbeh.2012.00083 · 3.27 Impact Factor
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    ABSTRACT: The circadian clock machinery is responsible for biological timekeeping on a systemic level. The central clock system controls peripheral clocks through a number of output cues that synchronize the system as a whole. There is growing evidence that changing cellular metabolic states have important effects on circadian rhythms and can thereby influence neuronal function and disease. Epigenetic control has also been implicated in the modulation of biological timekeeping, and cellular metabolism and epigenetic state seem to be closely linked. We discuss the idea that cellular metabolic state and epigenetic mechanisms might work through the circadian clock to regulate neuronal function and influence disease states.
    Nature Reviews Neuroscience 11/2012; 14(1). DOI:10.1038/nrn3393 · 31.43 Impact Factor
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