Photoperiodic modulation of the hepatic clock by the suprachiasmatic nucleus and feeding regime in mice.

Changes in photoperiod modulate the central circadian clock in the suprachiasmatic nucleus (SCN) as well as the peripheral clocks. Consequently, the SCN-driven output rhythms in activity and feeding are also modulated by the photoperiod. The aim of the present study was to elucidate whether photoperiodic modulation of the hepatic clock is mediated by changes in feeding or by another SCN-driven pathway. Five days after the change from short photoperiod (SP) to long photoperiod (LP), the profiles of Per2 and Rev-erbα expression in the rostral, middle and caudal regions of the SCN were desynchronized and those in the liver were modulated as in mice fully entrained to LP. The SCN profiles were not affected in mice left under SP and subjected to the 6-h night-time feeding regime for 5 days. In the liver, the profiles were shifted to the same phase, but their waveforms were not modulated compared with those under LP. In mice subjected to the change from SP to LP and fed twice daily during the daytime, the profiles in the SCN were not affected, whereas the waveforms and phases of those in the liver were affected. The data demonstrate that the adjustment of gene expression profiles in the rostral, middle and caudal SCN to the change from SP to LP proceeds within 5 days and is not affected by changes in the feeding regime. The results also suggest that the photoperiod-modulated SCN affects waveforms of gene expression profiles in the liver by food-independent signals.

Different mechanisms of adjustment to a change of the photoperiod in the suprachiasmatic and liver circadian clocks.

Changes in photoperiod modulate the circadian system, affecting the function of the central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The aim of the present study was to elucidate the dynamics of adjustment to a change of a long photoperiod with 18 h of light to a short photoperiod with 6 h of light of clock gene expression rhythms in the mouse SCN and in the peripheral clock in the liver, as well as of the locomotor activity rhythm. Three, five, and thirteen days after the photoperiod change, daily profiles of Per1, Per2, and Rev-erbalpha expression in the rostral, middle, and caudal parts of the SCN and of Per2 and Rev-erbalpha in the liver were determined by in situ hybridization and real-time RT-PCR, respectively. The clock gene expression rhythms in the different SCN regions, desynchronized under the long photoperiod, attained synchrony gradually following the transition from long to short days, mostly via advancing the expression decline. The photoperiodic modulation of the SCN was due not only to the degree of synchrony among the SCN regions but also to different waveforms of the rhythms in the individual SCN parts. The locomotor activity rhythm adjusted gradually to short days by advancing the activity onset, and the liver rhythms adjusted by advancing the Rev-erbalpha expression rise and Per2 decline. These data indicate different mechanisms of adjustment to a change of the photoperiod in the central SCN clock and the peripheral liver clock.

Influence of photoperiod duration and light-dark transitions on entrainment of Per1 and Per2 gene and protein expression in subdivisions of the mouse suprachiasmatic nucleus.

The circadian clock located within the suprachiasmatic nuclei (SCN) of the hypothalamus responds to changes in the duration of day length, i.e. photoperiod. Recently, changes in phase relationships among the SCN cell subpopulations, especially between the rostral and caudal region, were implicated in the SCN photoperiodic modulation. To date, the effect of abrupt, rectangular, light-to-dark transitions have been studied while in nature organisms experience gradual dawn and twilight transitions. The aim of this study was to compare the effect of a long (18 h of light) and a short (6 h of light) photoperiod with twilight relative to that with rectangular light-to-dark transition on the daily profiles of Per1 and Per2 mRNA (in situ hybridization) and PER1 and PER2 protein (immunohistochemistry) levels within the rostral, middle and caudal regions of the mouse SCN. Under the short but not under the long photoperiod, Per1, Per2 and PER1, PER2 profiles were significantly phase-advanced under the twilight relative to rectangular light-to-dark transition in all SCN regions examined. Under the photoperiods with rectangular light-to-dark transition, Per1 and Per2 mRNA profiles in the caudal SCN were phase-advanced as compared with those in the rostral SCN. The phase differences between the SCN regions were reduced under the long, or completely abolished under the short, photoperiods with twilight. The data indicate that the twilight photoperiod provides stronger synchronization among the individual SCN cell subpopulations than the rectangular one, and the effect is more pronounced under the short than under the long photoperiod.

Development of the light sensitivity of the clock genes Period1 and Period2, and immediate-early gene c-fos within the rat suprachiasmatic nucleus.

The molecular mechanism underlying circadian rhythmicity within the suprachiasmatic nuclei (SCN) of the hypothalamus has two light-sensitive components, namely the clock genes Per1 and Per2. Besides, light induces the immediate-early gene c-fos. In adult rats, expression of all three genes is induced by light administered during the subjective night but not subjective day. The aim of the present study was to ascertain when and where within the SCN the photic sensitivity of Per1, Per2 and c-fos develops during early postnatal ontogenesis. The specific aim was to find out when the circadian clock starts to gate photic sensitivity. The effect of a light pulse administered during either the subjective day or the first or second part of the subjective night on gene expression within the rat SCN was determined at postnatal days (P) 1, 3, 5 and 10. Per1, Per2 and c-fos mRNA levels were assessed 30 min, 1 and 2 h after the start of each light pulse by in situ hybridization histochemistry. Expression of Per1 and c-fos was light responsive from P1, and the responses began to be gated by the circadian clock at P3 and P10, respectively. Expression of Per2 was only slightly light responsive at P3, and the response was not fully gated until P5. These data demonstrate that the light sensitivity of the circadian clock develops gradually during postnatal ontogenesis before the circadian clock starts to control the response. The photoinduction of the clock gene Per2 develops later than that of Per1.

Maternal control of the fetal and neonatal rat suprachiasmatic nucleus.

The molecular clockwork underlying the generation of circadian rhythmicity within the suprachiasmatic nucleus (SCN) develops gradually during ontogenesis. The authors' previous work has shown that rhythms in clock gene expression in the rat SCN are not detectable at embryonic day (E) 19, start to form at E20 and develop further via increasing amplitude until postnatal day (P) 10. The aim of the present work was to elucidate whether and how swiftly the immature fetal and neonatal molecular SCN clocks can be reset by maternal cues. Pregnant rats maintained under a light-dark (LD) regimen with 12 h of light and 12 h of darkness were exposed to a 6-h delay of the dark period and released into constant darkness at different stages of the fetal SCN development. Adult rats maintained under the same LD regimen were exposed to an identical shifting procedure. Daily rhythms in spontaneous c-fos, Avp, Per1, and Per2 expression were examined within the adult and newborn SCN by in situ hybridization. Exposure of adult rats to the shifting procedure induced a significant phase delay of locomotor activity within 3 days after the phase shift as well as a delay in the rhythms of c-fos and Avp expression within 3 days and Per1 and Per2 expression within 5 days. Exposure of pregnant rats to the shifting procedure at E18, but not at E20, delayed the rhythm in c-fos and Avp expression in the SCN of newborn pups at P0-1. The shifting procedure at E20 did, however, induce a phase delay of Per1 and Per2 expression rhythms at P3 and P6. Hence, 5 days were necessary for phase-shifting the pups' SCN clock by maternal cues, be it the interval between E18 and P0-1 or the interval between E20 and P3, while only 3 days were necessary for phase-shifting the maternal SCN by photic cues. These results demonstrate that the SCN clock is capable of significant phase shifts at fetal developmental stages when no or very faint molecular oscillations can be detected.