Visual sensitivities of nur77 (NGFI-B) and zif268 (NGFI-A) induction in the suprachiasmatic nucleus are dissociated from c-fos induction and behavioral phase-shifting responses

Abstract

Mammalian circadian rhythms are regulated by a pacemaker in the suprachiasmatic nucleus of the hypothalamus. Recent work from several laboratories has shown that light induces the IEGs, c-fos and jun-B, in the rodent suprachiasmatic nucleus. In hamsters, there is a strong correlation between circadian entrainment and the induction of c-fos and jun-B in the suprachiasmatic nucleus by light. Previous work has shown that the IEGs, nur77 and zif268, both of which encode transcription factors, are also light-inducible in the rat suprachiasmatic nucleus [Rusak, B., McNaughton, L., Robertson, H.A. and Hunt, S.P., Circadian variation in photic regulation of IEG mRNAs in rat suprachiasmatic nucleus cells, Mol. Brain Res., 14 (1992) 124-130.; Sutin, E.L. and Kilduff, T.S., Circadian and light-induced expression of IEG mRNAs in the rat suprachiasmatic nucleus, Mol. Brain Res., 15 (1992) 281-290.]. To characterize the photic-regulation of these genes in the suprachiasmatic nucleus of golden hamsters, we used in situ hybridization to measure nur77 and zif268 mRNA levels with 33P-labeled complementary RNA probes. 5-min monochromatic light pulses at CT19 induced a dramatic increase in both nur77 and zif268 mRNA levels. Peak mRNA levels occurred 45-60 min after light onset for both nur77 and zif268. In addition, the induction of both nur77 and zif268 mRNA levels was gated by the circadian pacemaker. Light pulses during subjective day (CT3 and CT9), which do not cause behavioral phase-shifts, did not significantly alter mRNA levels of either nur77 or zif268; whereas light pulses during the subjective night (CT14 and CT19), which induce phase-shifts, dramatically increased both nur77 and zif268 mRNA levels. In contrast to c-fos induction, which has a photic threshold indistinguishable from that of the behavioral phase-shifting response, nur77 and zif268 mRNA induction were found to have visual sensitivities greater than the phase-shifting response by 1-2 log units (10-100-fold). Although light and circadian phase regulate nur77 and zif268 expression in the SCN, these results demonstrate that their induction is not rate-limiting for photic entrainment of the hamster circadian system.