Temporal Dynamics of Mouse Hippocampal Clock Gene Expression Support Memory Processing

Hippocampus. 2010 Mar;20(3):377-88. doi: 10.1002/hipo.20637.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / genetics
  • ARNTL Transcription Factors / metabolism
  • Animals
  • Biological Clocks / genetics
  • CLOCK Proteins / genetics
  • CLOCK Proteins / metabolism
  • Circadian Rhythm / genetics
  • Circadian Rhythm Signaling Peptides and Proteins / genetics*
  • Circadian Rhythm Signaling Peptides and Proteins / metabolism
  • Cryptochromes / genetics
  • Cryptochromes / metabolism
  • Gene Expression Regulation / physiology
  • Hippocampus / metabolism*
  • Hippocampus / physiopathology
  • Immunohistochemistry
  • Male
  • Memory / physiology*
  • Memory Disorders / genetics
  • Mice
  • Mice, Inbred C3H
  • Mice, Knockout
  • Period Circadian Proteins / genetics*
  • Period Circadian Proteins / metabolism
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Time Perception / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • ARNTL Transcription Factors
  • Arntl protein, mouse
  • Circadian Rhythm Signaling Peptides and Proteins
  • Cry1 protein, mouse
  • Cryptochromes
  • Per1 protein, mouse
  • Period Circadian Proteins
  • RNA, Messenger
  • Transcription Factors
  • CLOCK Proteins
  • Clock protein, mouse