Daily rhythm of spontaneous immediate-early gene expression in the rat suprachiasmatic nucleus.

Nocturnal light induces the expression of various immediate-early genes (IEGs) in the suprachiasmatic nucleus (SCN), the primary pacemaker of the circadian system of mammals, and causes phase shifts of behavioral rhythms. In the hamster SCN, some IEGs show both sensitivity to light induction at night and a daily peak of spontaneous expression near dawn in different regions of the nucleus. To investigate whether both patterns of IEG expression are observed in the rat SCN, the authors studied the expression of NGFI-A, junB, c-fos, and fosB near the time of subjective dawn in rats entrained to a light-dark 12:12 cycle and then maintained in constant total darkness for approximately 48 h. They found that there were two independent rhythms of expression for junB and c-fos mRNAs in the SCN: (1) a rhythm of photic sensitivity expressed throughout the night and (2) a spontaneous rhythm of expression triggered around dawn and persisting for at least 2 h into the day. By contrast, fosB and NGFI-A transcripts were expressed only after light exposure at night and did not exhibit significant levels of spontaneous expression in the absence of photic input. These observations demonstrate that the circadian clock gates expression of two independent rhythms related to IEG expression in the rat SCN. The rhythm of sensitivity to nocturnal light exposure is expressed more strongly in the ventral SCN and may be related to photic entrainment. The second rhythm is triggered spontaneously in darkness around subjective dawn and is expressed in more dorsal parts of the SCN.

Circadian and photic regulation of immediate-early gene expression in the hamster suprachiasmatic nucleus.

The hypothalamic suprachiasmatic nucleus is the site of an endogenous circadian clock synchronized by daily light-dark cycles. At some daily phases, light exposure both shifts the clock and alters the expression of several immediate-early genes in cells of the suprachiasmatic nucleus. We have studied both spontaneous circadian and light-induced expression of several immediate-early gene messenger RNAs and proteins in hamsters in constant darkness or in response to brief light exposure. There was no detectable spontaneous expression of NGFI-A messenger RNA in suprachiasmatic nucleus cells at any circadian phase, but light pulses induced its expression selectively during the subjective night, with highest levels of expression 6 h into the night. We also found that there are two independent rhythms of expression of junB messenger RNA and JunB protein, as well as c-fos messenger RNA and c-Fos protein, in the suprachiasmatic nucleus of hamsters: a rhythm of photic sensitivity expressed throughout the night and a spontaneous rhythm of expression triggered around dawn. Induction of NGFI-A messenger RNA and c-fos messenger RNA and c-Fos protein in response to a light pulse were found throughout the suprachiasmatic nucleus, with the highest levels of expression in the ventrolateral subdivision; however, the spontaneous expression of JunB and c-Fos proteins was confined mainly to the dorsomedial suprachiasmatic nucleus. The temporal and anatomical differences in the expression of these immediate-early genes in the mammalian suprachiasmatic nucleus suggest that their protein products may be involved in different signaling mechanisms mediating either photic entrainment or endogenous oscillations within distinct subpopulations of suprachiasmatic nucleus cells.

Differential effects of glutamatergic blockade on circadian and photic regulation of gene expression in the hamster suprachiasmatic nucleus.

Nocturnal light exposure induces immediate-early gene (IEG) expression in the hypothalamic suprachiasmatic nucleus (SCN) and causes phase shifts of activity rhythms in mammals. Some IEGs also show a circadian rhythm of expression in the SCN. While excitatory amino acids (EAAs) are known to be involved in mediating photic regulation of entrainment and gene expression, their involvement in spontaneous rhythms of gene expression has not been studied. We assessed the role of NMDA receptors in the expression of NGFI-A, junB and fosB mRNAs induced by light pulses of different intensities late in the night (Zeitgeber Time [ZT] 18). We also examined the spontaneous expression of junB mRNA near subjective dawn (ZT 0). Both dim (5 lx) and bright (100 lx) light pulses induced similar levels of expression of NGFI-A and junB in the SCN late in the night. fosB mRNA was strongly induced by bright light but was less sensitive to dim light. At ZT 18, dizocilpine (MK-801) (3 mg/kg, i.p. ), a non-competitive NMDA receptor antagonist, almost completely blocked light-evoked expression of IEG mRNAs in the ventral SCN but not in the dorsolateral region at a mid-caudal level using either light intensity. At ZT 0, MK-801 strongly reduced light-evoked expression of junB mRNA in both SCN subdivisions, but inhibited spontaneous expression significantly only in the dorsal region. NMDA receptors appear to play an important role in mediating photic input regulating IEG expression only in the ventral SCN at night. At dawn, however, NMDA receptors are involved in mediating photic effects in both parts of the SCN, as well as being involved in spontaneous activation of junB expression selectively in the dorsal SCN. These findings support the idea that the effects in the dorsolateral SCN of nocturnal light exposure are mediated by different mechanisms than those in other portions of the nucleus.