Abstract

Circadian rhythms are driven by clocks and oscillators, which are distributed throughout the brain and body, and rely on daily rhythms in the expression of canonical clock genes such as Period1 (PER1) and Period2 (PER2). In rodents, restricted feeding (RF) schedules limit food-access to a single meal each day and entrain circadian rhythms in food-anticipatory activity. The dorsomedial hypothalamic nucleus (DMH) is one brain area where daily rhythms in PER1 and PER2 are adjusted in response to RF, and this shift is potentially involved in generating food-entrained rhythms in behavior. The limbic forebrain, which is important in the regulation of motivation and emotion, also exhibits daily rhythms of PER2 expression that are adjusted by RF. The elucidation of RF-induced changes in the daily rhythm of PER1 and PER2 expression not only helps to identify brain areas that could be involved in the generation of food-entrained circadian rhythms, but also helps to define the nature and importance of these region-specific circadian rhythms. The experiments in the present thesis use male Wistar rats in order to study RF-induced changes of daily rhythms of PER1 and PER2 protein expression in the DMH, limbic forebrain and the “master” light-entrained clock, the suprachiasmatic nucleus (SCN). These studies demonstrate a nucleus-specific response to RF, which is associated with to the start-time, predictability, and duration of the daily RF meal. In the DMH, RF-induced rhythms of PER1 and PER2 expression were not strictly food-entrained, nor were they associated with the generation of circadian rhythms in food-anticipatory running-wheel activity. In the limbic forebrain, daily rhythms of PER2 expression in the oval nucleus of the bed nucleus of the stria terminalis (BNSTov) and the central nucleus of the amygdala (CEA) appeared to become food-entrained. Also in the limbic forebrain, daily rhythms of PER2 expression in the basolateral amygdala (BLA) and dentate gyrus (DG) were adjusted in response to daytime food-access, which is a novel feeding time for these nocturnal rodents. Finally, daily rhythms of PER1 and PER2 expression in the SCN failed to respond to RF and, instead, remained in synchrony with the environmental light-dark cycle. In summary, these studies show that RF has widespread effects on the daily rhythms of PER1 and PER2 expression in brain areas that are not traditionally linked to the regulation of circadian rhythms, per se, but are instead associated with the regulation of motivation, arousal, emotion, and learning.