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

Brain Struct Funct. 2013 Mar;218(2):551-62. doi: 10.1007/s00429-012-0415-4. Epub 2012 Apr 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Circadian Rhythm Signaling Peptides and Proteins / genetics
  • Circadian Rhythm Signaling Peptides and Proteins / metabolism*
  • Circadian Rhythm*
  • Gene Expression Regulation
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Neocortex / cytology
  • Neocortex / metabolism*
  • Neural Pathways / cytology
  • Neural Pathways / metabolism
  • Neurons / metabolism*
  • Period Circadian Proteins / genetics
  • Period Circadian Proteins / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Suprachiasmatic Nucleus / cytology
  • Suprachiasmatic Nucleus / metabolism
  • Time Factors

Substances

  • Circadian Rhythm Signaling Peptides and Proteins
  • Per2 protein, rat
  • Period Circadian Proteins
  • RNA, Messenger