Daily variation of CNS gene expression in nocturnal vs. diurnal rodents and in the developing rat brain

Bruce F. O'Hara, Fiona L. Watson, Rozi Andretic, Steven W. Wiler, Kimberly A. Young, Louise Bitting, H. Craig Heller, Thomas S. Kilduff

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Expression of c-fos has been shown to vary throughout the brain over the course of the 24-h day. The magnitude of these changes appear to be similar in a light:dark (LD) cycle or in constant dark (DD). To further examine whether the diurnal and circadian changes in c-fos and other immediate-early gene (IEC) expression in brain are related to waking behaviors such as locomotor activity, we conducted three experiments using Northern analysis. First, we compared IEG expression in nocturnal vs. diurnally active species. Second, we investigated IEG expression in a hibernating species during its active and inactive phases. Third, we examined the development of IEG expression in the young post-natal rat. As a comparison to results obtained in extra-SCN brain regions, we also examined IEG and vasopressin expression in the SCN itself across the circadian cycle. Animals maintained under a 12:12-h LD cycle were sacrificed in the morning (10:00-11:00 h, ZT2-ZT3) or night (22:00-23:00 h, ZT14-ZT15) or at the corresponding circadian times (CT) when kept in DD. Rats sacrificed in the morning always showed lower c-fos expression than at night in all brain areas examined while the reverse pattern was seen in squirrels under both LD and DD conditions, suggesting a direct correlation between c-fos message and activity. The cerebellum displayed the greatest magnitude change between morning and night (often reaching 10-fold). Among other IEGs examined, the expression of NGFI-A and junB are similar to c-fos, but of lesser magnitude, whereas c-jun appears to be invariant in the rat but is increased during the active phase in squirrels. During the hibernation season, squirrels have lower levels of c-fos consistent with their low levels of activity even during their euthermic interbout periods. c-fos expression in the cerebellum and rest of brain of 1-week-old rats sacrificed at ZT3 and ZT15 showed low levels at both timepoints whereas 2- and 3-week-old animals had higher levels at night as do adults. Among other IEGs, junB and NGFI-A again were similar to c-fos while c-jun and junD were more constant. Our observations support the idea of a diurnal rhythm of IEG expression in the CNS that is related to waking behaviors. Among IEGs, c-fos exhibits the greatest daily variation in expression.

Original languageEnglish
Pages (from-to)73-86
Number of pages14
JournalMolecular Brain Research
Issue number1
StatePublished - Aug 1997

Bibliographical note

Funding Information:
We thank Dr. Norman (Bud) Ruby for assistance and advice in the experiments using squirrels and Ms. May Chin for help with the manuscript. We would also like to thank Drs. Daniel Nathans, Tom Curran, Jeffrey Milbrandt, Elaine Fuchs and Thomas Sherman for providing cDNAs. This work was supported by NIH Grants P50 HD29732, P01 AG11084 and K21 DA00187.


  • Circadian rhythm
  • Immediate-early gene
  • PolyA tail
  • Vasopressin
  • c-fos

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience


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