Temporal dynamics of mouse hippocampal clock gene expression support memory processing

Hippocampal plasticity and mnemonic processing exhibit a striking time‐of‐day dependence and likely implicate a temporally structured replay of memory traces. Molecular mechanisms fulfilling the requirements of sensing time and capturing time‐related information are coded in dynamics of so‐called clock genes and their protein products, first discovered and described in the hypothalamic suprachiasmatic nucleus. Using real‐time PCR and immunohistochemical analyses, we show that in wildtype mice core clock components (mPer1/PER1, mPer2/PER2, mCry1/CRY1, mCry2/CRY2, mClock/CLOCK, mBmal1/BMAL1) are expressed in neurons of all subregions of the hippocampus in a time‐locked fashion over a 24‐h (diurnal) day/night cycle. Temporal profiling of these transcriptional regulators reveals distinct and parallel peaks, at times when memory traces are usually formed and/or consolidated. The coordinated rhythmic expression of hippocampal clock gene expression is greatly disordered in mice deficient for the clock gene mPer1, a key player implicated in both, maintenance and adaptative plasticity of circadian clocks. Moreover, Per1‐knockout animals are severely handicapped in a hippocampus‐dependent long‐term spatial learning paradigm. We propose that the dynamics of hippocampal clock gene expression imprint a temporal structure on memory processing and shape at the same time the efficacy of behavioral learning. © 2009 Wiley‐Liss, Inc.