Distinct phase relationships between suprachiasmatic molecular rhythms, cerebral cortex molecular rhythms, and behavioral rhythms in early runner (CAST/EiJ) and nocturnal (C57BL/6J) mice

Peng Jiang, Kathleen M. Franklin, Marilyn J. Duncan, Bruce F. O'Hara, Jonathan P. Wisor*

*Corresponding author for this work

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Study Objective: We have previously established that CAST/EiJ (CAST) mice differ from normal mice, such as C57BL/6J (B6), in the timing of wheel-running onset relative to light/dark cycles. These mice provide an animal model for studies of the genetic and neurobiological basis for circadian phase misalignment in humans. Neither differences in endogenous circadian period nor the shape of the photic phase response curve explain the difference in the timing of activity onset between CAST and B6 mice, suggesting a mechanism downstream of the circadian clock. Here, we further test the hypothesis that the two strains differ with respect to circadian oscillations at the molecular level. Design: Sleep/wake cycles were examined and rhythms of Period1 (Per1) and Period2 (Per2) expression were measured in the cerebral cortex, suprachiasmatic nucleus (SCN), and other hypothalamic regions. Setting: Basic sleep and molecular research laboratory. Patients or Participants: Male mice of the B6 and CAST inbred strains. Interventions: None. Measurements and Results: Sleep/wake cycles were advanced by approximately 4 h in CAST mice relative to B6 mice. This was paralleled by phase-advanced rhythms of Per1 and Per2 expression, as measured by in situ hybridization, in the cerebral cortex of CAST relative to B6. By contrast, the timing of circadian oscillations and the photic induction of Per1 and Per2 expression in the SCN were unaffected by strain. Conclusion: The advanced phase of wheel running and sleep/wake cycles in CAST mice relative to B6 mice is apparently not associated with differences in molecular oscillations in the SCN clock itself, but most likely in mechanisms downstream of the SCN clock. CAST mice may therefore provide a model system to investigate circadian downstream mechanisms underlying unusual patterns of entrainment to the ambient photoperiod.

Original languageEnglish (US)
Pages (from-to)1385-1394
Number of pages10
JournalSleep
Volume35
Issue number10
DOIs
StatePublished - Oct 1 2012

Keywords

  • Advanced sleep phase syndrome
  • Circadian
  • Paraventricular nucleus
  • Per expression
  • Subparaventricular zone

ASJC Scopus subject areas

  • Clinical Neurology
  • Physiology (medical)

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