Expression of the Circadian Clock Gene Period2 in the Hippocampus: Possible Implications for Synaptic Plasticity and Learned Behaviour

Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024-1759, USA.
ASN Neuro (Impact Factor: 4.02). 02/2009; 1(3). DOI: 10.1042/AN20090020
Source: PubMed


Genes responsible for generating circadian oscillations are expressed in a variety of brain regions not typically associated with circadian timing. The functions of this clock gene expression are largely unknown, and in the present study we sought to explore the role of the Per2 (Period 2) gene in hippocampal physiology and learned behaviour. We found that PER2 protein is highly expressed in hippocampal pyramidal cell layers and that the expression of both protein and mRNA varies with a circadian rhythm. The peaks of these rhythms occur in the late night or early morning and are almost 180° out-of-phase with the expression rhythms measured from the suprachiasmatic nucleus of the same animals. The rhythms in Per2 expression are autonomous as they are present in isolated hippocampal slices maintained in culture. Physiologically, Per2-mutant mice exhibit abnormal long-term potentiation. The underlying mechanism is suggested by the finding that levels of phosphorylated cAMP-response-element-binding protein, but not phosphorylated extracellular-signal-regulated kinase, are reduced in hippocampal tissue from mutant mice. Finally, Per2-mutant mice exhibit deficits in the recall of trace, but not cued, fear conditioning. Taken together, these results provide evidence that hippocampal cells contain an autonomous circadian clock. Furthermore, the clock gene Per2 may play a role in the regulation of long-term potentiation and in the recall of some forms of learned behaviour.

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Available from: Takashi Kudo
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    • "The clock genes are associated with the regulation of circadian rhythms (Brancaccio et al., 2014) and are expressed in the suprachiasmatic nucleus as well as several other brain regions, including the hippocampus (Kyriacou and Hastings, 2010). Animal work illustrates that mice without clock genes, Period1 or Period2, show impaired hippocampal-dependent learning (Jilg et al., 2010; Wang et al., 2009). In addition, old age is accompanied by significant alterations in CLOCK gene expression within the mouse hippocampus, which is thought to contribute to age-related disruptions in circadian rhythms (Wyse and Coogan, 2010). "
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    • "Thus, the local rhythms in PER2 could control the temporal program of the expression of other genes and proteins specific to the hippocampus, as recently demonstrated in the liver (Kornmann et al., 2007). Furthermore, the PER2 in the hippocampus may play a role in modulating neurogenesis (Borgs et al., 2009), the regulation of long-term potentiation (LTP), and the recall of some forms of learned behavior (Wang et al., 2009). A variety of studies suggest that learning and memory processes are sensitive to disruptions in sleep and circadian rhythms (Dijk et al., 1992; Ellenbogen et al., 2006; Peigneux Fig. 3 – Distributions of PV-IR, CB-IR and CR-IR neurons in the granular layer of the dentate gyrus of the primate Sapajus apella. "
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    • "(A.A. Nunez). local rhythmic expression of clock genes in areas of the brain outside of the SCN, (Abe et al., 2002) including the hippocampus (Duncan et al., 2013; Gilhooley et al., 2011; Ikeno et al., 2013; Lamont et al., 2005; Li et al., 2013; Otalora et al., 2013; Ramanathan et al., 2010b; Wang et al., 2009). These observations bring up the question of the role of hippocampal clock-gene expression in the regulation of hippocampaldependent cognitive functions. "
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