The suprachiasmatic nucleus (SCN) of the hypothalamus contains a circadian pacemaker that controls a variety of physiological and behavioral rhythms. Photic induction of immediate early genes such as c-fos in the SCN occurs in a circadian-phase dependent manner, suggesting that c-fos may be part of the pathway for entrainment of circadian rhythms. The purpose of this study was to determine the point in development when photic stimuli can first activate c-fos mRNA expression in the rat SCN. The results indicate that photic stimulation can induce statistically significant c-fos mRNA expression at circadian time 22 (CT22) on postnatal day 1 (P1), although hybridization above background levels can be detected in the SCN of some rat pups earlier in the subjective night. We infer that a multi-step pathway between visual transduction by the retina and regulation of c-fos transcription in SCN cells must be mature by CT22 on P1.
"Therefore, the characterization of the NMDAR subunits that constitute the receptor channels within the SCN may contribute to understanding the time-regulated NMDAR responses to photic as well as non-photic stimuli. Although the rat SCN is photosensitive immediately after birth, as demonstrated by photic induction of c-fos and Per1 expression (Leard et al., 1994; Matějů et al., in press), the photic entrainment of the circadian clock matures only gradually. During the prenatal and early postnatal period, the light/dark cycle entrains the circadian clock of fetuses and pups via the maternal pacemaker (El-Hennamy et al., 2008). "
[Show abstract][Hide abstract] ABSTRACT: The circadian rhythms of mammals are generated by the circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Its intrinsic period is entrained to a 24 h cycle by external cues, mainly by light. Light impinging on the SCN at night causes either advancing or delaying phase shifts of the circadian clock. N-methyl-d-aspartate receptors (NMDAR) are the main glutamate receptors mediating the effect of light on the molecular clockwork in the SCN. They are composed of multiple subunits, each with specific characteristics whose mutual interactions strongly determine properties of the receptor. In the brain, the distribution of NMDAR subunits depends on the region and developmental stage. Here, we report the circadian expression of the NMDAR1 subunit in the adult rat SCN and depict its splice variants that may constitute the functional receptor channel in the SCN. During ontogenesis, expression of two of the NMDAR1 subunit splice variants, as well as the NMDAR3A and 3B subunits, exhibits developmental loss around the time of eye opening. Moreover, we demonstrate the spatial and developmental characteristics of the expression of the truncated splice form of NMDAR1 subunit NR1-E in the brain. Our data suggest that specific properties of the NMDAR subunits we describe within the SCN likely influence the photic transduction pathways mediating the clock entrainment. Furthermore, the developmental changes in NMDAR composition may contribute to the gradual postnatal maturation of the entrainment pathways.
"Our data, which demonstrate the photosensitivity of the rat SCN already during the first postnatal day, are in accordance with earlier reports on c-fos photoinduction at this developmental stage (Leard et al., 1994). In the present study, light pulses at P1 affected not only c-fos expression as the neuronal activity marker but also the Fig. 6. "
[Show abstract][Hide abstract] ABSTRACT: 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.
European Journal of Neuroscience 03/2009; 29(3):490-501. DOI:10.1111/j.1460-9568.2009.06609.x · 3.18 Impact Factor
"The circadian clock starts to be sensitive to light soon after birth. Light induces expression of immediate-early gene c-fos and its protein cFos already in 1-day and 3-day rat pups, respectively  . Thus, light information reaches the SCN cells well before eyelid opening. "
[Show abstract][Hide abstract] ABSTRACT: The molecular mechanism underlying a generation of circadian rhythmicity within the suprachiasmatic nucleus (SCN) is based on interactive negative and positive feedback loops that drive the rhythmic transcription of clock genes and translation of their protein products. In adults, the molecular mechanism is affected by seasonal changes in day length, i.e., photoperiod. The photoperiod modulates phase, waveform, and amplitude of the rhythmic clock genes expression as well as the phase relationship between their profiles. To ascertain when and how the photoperiod affects the circadian core clock mechanism during ontogenesis, the rhythmic expression of clock genes, namely of Per1, Per2, Cry1 and Bmal1 was determined in 3-, 10- and 20-day-old rat pups maintained under either a long photoperiod with 16 h of light and 8 h of darkness per day (LD 16:8) or under a short, LD 8:16 photoperiod. The daily profiles in the level of clock genes mRNA were studied in constant darkness. The photoperiod affected the profile of Per1 and Per2 mRNA in 20- and 10- but not yet in 3-day-old pups. Expression of Cry1 was affected only in 20-day-old pups, whereas expression of Bmal1 was not yet affected even in 20-day-old rats. The results demonstrate no effect of the photoperiod on 3-day-old pups, only partial entrainment of the molecular core clockwork in 10-day-old pups and a more mature, though not yet fully complete, entrainment in 20-day-old pups as compared with adult animals. The developmental interval when the photoperiod begins to entrain the core clock mechanism completely might thus occur around the time of weaning.
Brain Research 01/2006; 1064(1-2):83-9. DOI:10.1016/j.brainres.2005.10.022 · 2.84 Impact Factor
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