The central and basolateral nuclei of the amygdala exhibit opposite diurnal rhythms of expression of the clock protein Period2

Abstract

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...

Forebrain oscillators ticking with different clock hands

“…2B and 3B). Data obtained for PER2 expression in BLA confirm previous results gathered in rats (Lamont et al, 2005).…”

“…For instance, rhythmic expression of Per1 and Per2 mRNA is observed in forebrain structures such as olfactory bulbs, piriform and cerebral cortices, hippocampus, paraventricular and arcuate hypothalamic nuclei (Asai et al, 2001;Wakamatsu et al, 2001;Abe et al, 2002;Granados-Fuentes et al, 2004). PER2 expression has also been reported in limbic structures, such as amygdala and bed nucleus of the stria terminalis (Amir et al, 2004;Lamont et al, 2005). Except for the SCN in which the rhythm of PERs follows the mRNA expression by 4-6 h (Field et al, 2000;Mendoza et al, 2007), little is known about the exact timing of both PER1 and PER2 oscillations in forebrain structures.…”

“…Whereas light is the principal synchronizer for the SCN, Per oscillations in extra-SCN brain regions can be affected by feeding cues (Wakamatsu et al, 2001;Lamont et al, 2005;AngelesCastellanos et al, 2007). Restricted feeding can produce changes in physiology and behavior which are even more marked in response to hypocaloric feeding (HF) (Challet et al, 2003;Mendoza et al, 2005b;Feillet et al, 2006).…”

Glucocorticoids and circadian clock control of cell proliferation: At the interface between three dynamic systems

“…The interaction of glucocorticoid and circadian clock control of cell proliferation may not be limited to one single mechanism, given the diverse effects of glucocorticoids on cell proliferation in different tissues. As mentioned above, a similar situation exists for the contribution of glucocorticoids to circadian clock gene cycling in different tissues: While circadian per2 expression in some regions of the brain depends on glucocorticoids [111,112], this is not the case in other brain regions [112] or the liver [44,114]. Clearly, similar tissue specific differences might also be at work in the control of circadian cell cycle rhythms by glucocorticoids, with rhythmic glucocorticoid presence required in some tissues and tonic levels being sufficient in others.…”

“…However, mice lacking the glucocorticoid receptor in the liver still exhibit phases of clock gene expression identical to those of their wild type siblings, arguing against a strict requirement for glucocorticoids in liver clock entrainment [44]. Nevertheless, glucocorticoids do appear to be required for normal circadian expression of per2 in some areas of the brain, since cycling M a n u s c r i p t expression of this gene is abolished in adrenalectomised animals (animals in which the adrenal gland has been removed) [111,112]. Interestingly, the per2 rhythms can resume when diurnal changes in corticosterone are restored in adrenalectomised animals by delivering corticosterone with the drinking water.…”