Phase differences in expression of circadian clock genes in the central nucleus of the amygdala, dentate gyrus, and suprachiasmatic nucleus in the rat.

We performed a high temporal resolution analysis of the transcript level of two core clock genes, Period2 (Per2) and Bmal1, and a clock output gene, Dbp, in the suprachiasmatic nucleus (SCN), the master circadian clock, and in two forebrain regions, the lateral part of the central nucleus of the amygdala (CEAl), and dentate gyrus (DG), in rats. These regions, as we have shown previously, exhibit opposite rhythms in expression of the core clock protein, PERIOD2 (PER2). We found that the expression of Per2, Bmal1 and Dbp follow a diurnal rhythm in all three regions but the phase and amplitude of the rhythms of each gene vary across regions, revealing important regional differences in temporal dynamics underlying local daily rhythm generation in the mammalian forebrain.

Comprehensive mapping of regional expression of the clock protein PERIOD2 in rat forebrain across the 24-h day.

In mammals, a light-entrainable clock located in the suprachiasmatic nucleus (SCN) regulates circadian rhythms by synchronizing oscillators throughout the brain and body. Notably, the nature of the relation between the SCN clock and subordinate oscillators in the rest of the brain is not well defined. We performed a high temporal resolution analysis of the expression of the circadian clock protein PERIOD2 (PER2) in the rat forebrain to characterize the distribution, amplitude and phase of PER2 rhythms across different regions.

Peripheral circadian clocks--a conserved phenotype?

The circadian system of mammals regulates the timing of occurrence of behavioral and physiological events, thereby optimizing adaptation to their surroundings. This system is composed of a single master pacemaker located in the suprachiasmatic nucleus (SCN) and a population of peripheral clocks. The SCN integrates time information from exogenous sources and, in turn, synchronizes the downstream peripheral clocks.

Variations in daily expression of the circadian clock protein, PER2, in the rat limbic forebrain during stable entrainment to a long light cycle.

The circadian clock in the mammalian suprachiasmatic nucleus (SCN) can be entrained by light cycles longer than the normal 24-h light/dark (LD) cycle, but little is known about the effect of such cycles on circadian clocks outside the SCN. Here we examined the effect of exposure to a 26-h T cycle (T26, 1 h:25 h LD) on patterns of expression of the clock protein, PERIOD2 (PER2), in the SCN and in four regions of the limbic forebrain known to exhibit robust circadian oscillations in PER2: the oval nucleus of the bed nucleus of the stria terminalis (BNSTov), central nucleus of the amygdala (CEA), basolateral amygdala (BLA), and dentate gyrus (DG). All rats showed stable entrainment of running wheel activity rhythms to the T26 cycle.

The expression of the clock protein PER2 in the limbic forebrain is modulated by the estrous cycle.

Daily behavioral and physiological rhythms are linked to circadian oscillations of clock genes in the brain and periphery that are synchronized by the master clock in the suprachiasmatic nucleus. In addition, there are a number of inputs that can influence circadian oscillations in clock gene expression in a tissue-specific manner. Here we identify an influence on the circadian oscillation of the clock protein PER2, endogenous changes in ovarian steroids, within two nuclei of the limbic forebrain: the oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala.

Pinealectomy does not affect diurnal PER2 expression in the rat limbic forebrain.

A role for the pineal hormone, melatonin, in the regulation of the rhythmic expression of circadian clock genes is suggested by the finding that surgical removal of the pineal gland abolishes the rhythm of expression of clock genes such as Per1 in several neural and endocrine tissues in rodents, including the caudate-putamen (CP) and nucleus accumbens, the hypophyseal pars tuberalis and adrenal cortex. Pinealectomy has no effect on clock gene rhythms in the suprachiasmatic nucleus (SCN), the master circadian clock, as well as in the eyes and heart, indicating that the effect of melatonin on clock gene rhythms is tissue specific. To further study the role of melatonin in the regulation of the rhythm of clock genes, we assessed in rats the effect of pinealectomy on the rhythm of expression of the clock protein, PER2, in a number of key limbic forebrain structures, the oval nucleus of the bed nucleus of the stria terminalis (BNST-OV), the central nucleus of the amygdala (CEA) and the hippocampus (HIPP).