ORIGINAL ARTICLE Circadian clock components in the rat neocortex: daily dynamics, localization and regulation Martin F. Rath • Kristian Rohde • Jan Fahrenkrug • Morten Møller Received: 1 March 2012 / Accepted: 3 April 2012 / Published online: 21 April 2012 Ó Springer-Verlag 2012 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 autoregula- tory network with clock gene products as core elements. Recent investigations have shown the presence of periph- eral clocks in extra-hypothalamic areas of the central ner- vous 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 neo- cortical 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 neo- cortex 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 Á Circadian rhythm Á Clock gene Á Peripheral oscillator Á 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 Introduction Circadian rhythms are endogenous rhythms with a period that closely approximates the 24-h period of the day. In mammals, the main circadian timekeeper resides in the suprachiasmatic nucleus (SCN) of the hypothalamus (Moore and Eichler 1972; Stephan and Zucker 1972). The majority of neurons in the SCN are capable of generating an endogenous circadian rhythm in firing rate (Welsh et al. 1995), but light acts to synchronize this endogenous clock to ambient light–dark conditions via the retino-hypotha- lamic projection (Moore and Lenn 1972; Klein and Moore 1979; Gooley et al. 2001; Hannibal et al. 2002; Hattar et al. 2003; Guilding and Piggins 2007; Klein et al. 2010). At the molecular level, the current circadian clockwork model depicts a transcriptional/posttranslational autoregu- latory feedback loop with clock gene products as core elements (Reppert and Weaver 2002; Hastings et al. 2008; Zhang and Kay 2010). The clock genes encode transcrip- tional modulators, whose expression level, dimerization and Electronic supplementary material The online version of this article (doi:10.1007/s00429-012-0415-4) contains supplementary material, which is available to authorized users. M. F. Rath (&) Á K. Rohde Á M. Møller Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Panum Institute 24.2, Blegdamsvej 3, 2200 Copenhagen, Denmark e-mail: mrath@sund.ku.dk J. Fahrenkrug Department of Clinical Biochemistry, Faculty of Health and Medical Sciences, University of Copenhagen, Bispebjerg Hospital, 2400 Copenhagen, Denmark 123 Brain Struct Funct (2013) 218:551–562 DOI 10.1007/s00429-012-0415-4