Persistence of a behavioral food-anticipatory circadian rhythm following dorsomedial hypothalamic ablation in rats. Am J Physiol Regul Integr Comp Physiol 290: R1527-R1534, 2006. First published January 19, 2006 doi:10.1152/ajpregu.00874.2005.-Circadian rhythms of behavior in rodents are regulated by a system of circadian oscillators, including a master light-entrainable pacemaker in the suprachiasmatic nucleus that mediates synchrony to the day-night cycle, and food-entrainable oscillators located elsewhere that generate rhythms of food-anticipatory activity (FAA) synchronized to daily feeding schedules. Despite progress in elucidating neural and molecular mechanisms of circadian oscillators, localization of food-entrainable oscillators driving FAA remains an enduring problem. Recent evidence suggests that the dorsomedial hypothalamic nucleus (DMH) may function as a final common output for behavioral rhythms and may be critical for the expression of FAA (Gooley JJ, Schomer A, and Saper CB. Nat Neurosci 9: 398 -407, 2006). To determine whether the reported loss of FAA by DMH lesions is specific to one behavioral measure or generalizes to other measures, rats received large radiofrequency lesions aimed at the DMH and were recorded in cages with movement sensors. Total and partial DMH ablation was associated with a significant attenuation of light-dark-entrained activity rhythms during ad libitum food access, because of a selective reduction in nocturnal activity. When food was restricted to a single 3-h daily meal in the middle of the lights-on period, all DMH and intact rats exhibited significant FAA. The rhythm of FAA persisted during a 48-h food deprivation test and reappeared during a 72-h deprivation test after ad libitum food access. The DMH is not the site of oscillators or entrainment pathways necessary for all manifestations of FAA, but may participate on the output side of this circadian function. food entrainment; food-anticipatory activity; food-entrainable oscillator CIRCADIAN RHYTHMS IN MAMMALS are generated by a system of cell-autonomous circadian oscillators distributed within the brain and in peripheral organs (32,57). A population of oscillators located in the retino-recipient hypothalamic suprachiasmatic nucleus (SCN) function as a master pacemaker critical for normal circadian organization of behavior and physiology and for entrainment of rhythms to daily light-dark (LD) cycles (34). Circadian rhythms can also be entrained by daily feeding schedules. If food access is restricted to a narrow daily temporal window (typically 2-4 h in the middle of the lights-on period), nocturnal rodents, such as rats, mice, and hamsters, become behaviorally active in anticipation of the feeding time. This daily rhythm of food-anticipatory activity (FAA) takes a few circadian cycles to emerge, exhibits gradual shifting (transients) if mealtime is shifted, persists for at least 5 days during total food deprivation, and does not emerge if the interval between mealtimes is outside of the circadian range or its har...

Circadian rhythms in Syrian hamsters can be phase advanced by activity or arousal stimulated during the daily rest phase ("subjective day"). A widely used method for stimulating activity is confinement to a novel wheel. Some hamsters decline to run, and some procedures may reduce the probability of running. The authors evaluated food deprivation (FD) as a method to promote running. Given evidence that perturbations of cell metabolism or glucose availability may affect circadian clock function in some tissues or species, they also assessed the effects of FD on free-running circadian phase, resetting responses to photic and nonphotic stimuli and plasma glucose. In constant light, a 27-h fast significantly increased running in a novel wheel and marginally increased the average size of resulting phase shifts. FD, without novel wheel confinement, was associated with some very large phase shifts or disruption of rhythmicity in hamsters that spontaneously ran in their home wheels during the subjective day. Hamsters that ran only during the usual active phase (subjective night) or that were prevented from running did not exhibit phase shifts, despite refeeding in the mid-subjective day. Using an Aschoff Type II design for measuring shifts, a 27-h fast significantly increased the number of hamsters that ran continuously when confined to a novel wheel but did not affect the dose-response relation between the amount of running and the size of the resulting shift. A day of fasting also did not affect the size of phase delay or advance shifts to 30-min light pulses in the subjective night. Plasma glucose was markedly reduced by wheel running in combination with fasting but was increased by running in nonfasted hamsters. These results establish FD as a useful tool for stimulating activity in home cage or novel wheels and indicate that in Syrian hamsters, significant alterations in glucose availability, associated with running, fasting, and refeeding, have surprisingly little effect on circadian pacemaker function.