There is considerable evidence that circadian rhythms in mammals can be modulated by emotional state, but how emotional state modulates specific circadian outputs is poorly understood. We analyzed the expression of the circadian clock protein Period2 (PER2) in three regions of the limbic forebrain known to play key roles in emotional regulation, the central nucleus of the amygdala (CEA), the basolateral amygdala (BLA), and the dentate gyrus (DG). We report here that cells in all three regions exhibit daily rhythms in expression of PER2 that are under the control of the master clock, the suprachiasmatic nucleus (SCN). The rhythm in the CEA and the rhythms in the BLA and DG are diametrically opposite in phase and are differentially affected by adrenalectomy. Adrenalectomy completely abolished the PER2 rhythm in the CEA but had no effect on the PER2 rhythms in the BLA and DG. We previously reported a rhythm in PER2 expression in the oval nucleus of the bed nucleus of the stria terminalis that is identical in phase and sensitivity to adrenalectomy to that found in the CEA. Together, these findings show that key structures of the limbic forebrain exhibit daily oscillations in clock gene expression that are controlled not only by input from the SCN but, importantly, by hormonal and neurochemical changes that normally accompany motivational and emotional states. Thus, cells within these areas are strategically positioned to integrate the inputs from the SCN and emotional states to modulate circadian rhythms downstream from the SCN clock.hippocampus ͉ suprachiasmatic nucleus ͉ oval nucleus ͉ circadian clock I n mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus is recognized as a master clock responsible for the regulation of all behavioral and physiological circadian rhythms (1). The rhythm of the SCN, although sensitive to the daily cycle of light, is relatively invulnerable to environmental challenges and changes in physiology (2, 3). Yet it is recognized that stressors and changes in emotional states can have disruptive effects on behavioral and physiological rhythms (4-8). Furthermore, disruptions of circadian rhythms have negative effects on mood and well being, as observed during jet lag or shift work (9, 10).Although the SCN is the only clock structure required for the generation of circadian rhythmicity, recent studies show that circadian rhythms in expression of clock genes, such as Per1 and Per2, can be found in other brain regions that participate in the control of specific behavioral and physiological outputs. These include, but are not limited to, the striatum, paraventricular hypothalamic nucleus, arcuate nucleus, preoptic area, and olfactory bulbs (11-17). The study of clock genes in these and other functionally defined brain regions may help to determine how the SCN clock controls specific circadian rhythms and, importantly, may contribute to an understanding of how diverse experiences and pathological conditions can affect circadian rhythms downstream from the SCN clock.We found recently th...
