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Brain Structure and Function

, Volume 218, Issue 2, pp 551–562 | Cite as

Circadian clock components in the rat neocortex: daily dynamics, localization and regulation

  • Martin F. Rath
  • Kristian Rohde
  • Jan Fahrenkrug
  • Morten Møller
Original Article

Abstract

The circadian master clock of the mammalian brain resides in the suprachiasmatic nucleus (SCN) of the hypothalamus. At the molecular level, the clock of the SCN is driven by a transcriptional/posttranslational autoregulatory network with clock gene products as core elements. Recent investigations have shown the presence of peripheral clocks in extra-hypothalamic areas of the central nervous system. However, knowledge on the clock gene network in the cerebral cortex is limited. We here show that the mammalian clock genes Per1, Per2, Per3, Cry1, Cry2, Bmal1, Clock, Nr1d1 and Dbp are expressed in the rat neocortex. Among these, Per1, Per2, Per3, Cry1, Bmal1, Nr1d1 and Dbp were found to exhibit daily rhythms. The amplitude of circadian oscillation in neocortical clock gene expression was damped and the peak delayed as compared with the SCN. Lesions of the SCN revealed that rhythmic clock gene expression in the neocortex is dependent on the SCN. In situ hybridization and immunohistochemistry showed that products of the canonical clock gene Per2 are located in perikarya throughout all areas of the neocortex. These findings show that local circadian oscillators driven by the SCN reside within neurons of the neocortex.

Keywords

Cerebral cortex Circadian rhythm Clock gene Peripheral oscillator Suprachiasmatic nucleus 

Abbreviations

DD

Dark–dark lighting regime (constant darkness)

LD

Light–dark lighting regime

qPCR

Quantitative real-time reverse-transcription PCR

SCN

Suprachiasmatic nucleus

ZT

Zeitgeber time

Notes

Acknowledgments

This work was supported by the Danish Medical Research Council (grants number 271-09-0206 and 271-07-0412) and the Lundbeck Foundation (grant number R34-A3364). We wish to thank Ms. Tine Thorup Mellergaard for expert technical assistance.

Supplementary material

429_2012_415_MOESM1_ESM.pdf (444 kb)
Supplementary material 1 (PDF 444 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Martin F. Rath
    • 1
  • Kristian Rohde
    • 1
  • Jan Fahrenkrug
    • 2
  • Morten Møller
    • 1
  1. 1.Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Panum Institute 24.2CopenhagenDenmark
  2. 2.Department of Clinical Biochemistry, Faculty of Health and Medical Sciences, University of Copenhagen, Bispebjerg HospitalCopenhagenDenmark

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