Dentate gyrus-specific manipulation of β-Ca2+/calmodulin- dependent kinase II disrupts memory consolidation

Min H. Cho, Xiaohua Cao, Deheng Wang, Joe Z. Tsien

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Although the functions of α-Ca2+/calmodulin-dependent kinase II (CaMKII) have been studied extensively, the role of βCaMKII, a coconstituent of the CaMKII holoenzyme in synaptic plasticity, learning, and memory has not been examined in vivo. Here we produce a transgenic mouse line in which the inducible and reversible manipulation of βCaMKII activity is restricted to the hippocampal dentate gyrus, the region where long-term potentiation was originally discovered. We demonstrate that βCaMKII activity in the dentate gyrus selectively impaired long-term potentiation in the dentate perforant path, but not in the CA1 Schaffer collateral pathway. Although the transgenic mice showed normal 1-day memories, they were severely impaired in 10-day contextual fear memory. Systematic manipulations of dentate βCaMKII activity during various distinct memory stages further reveal the initial day within the postlearning consolidation period as a critical time window that is highly sensitive to changes in βCaMKII activity. This study provides evidence not only for the functional role of βCaMKII in the dentate gyrus plasticity and hippocampal memory, but also for the notion that the mismatch between the actual learning pattern and reactivation patterns in the dentate gyrus circuit can underlie long-term memory consolidation.

Original languageEnglish (US)
Pages (from-to)16317-16322
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number41
StatePublished - Oct 9 2007
Externally publishedYes


  • Long-term memory
  • Long-term potentiation
  • Pharmacogenetic
  • Protein knockout

ASJC Scopus subject areas

  • General


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