Circadian clock components in the rat neocortex: daily dynamics, localization and regulation
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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.
KeywordsCerebral cortex Circadian rhythm Clock gene Peripheral oscillator Suprachiasmatic nucleus
Dark–dark lighting regime (constant darkness)
Light–dark lighting regime
Quantitative real-time reverse-transcription PCR
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.
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