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

被引:25
作者
Cho, Min H.
Cao, Xiaohua
Wang, Deheng
Tsien, Joe Z. [1 ]
机构
[1] Med Coll Georgia, Dept Neurol, Augusta, GA 30912 USA
[2] Boston Univ, Ctr Syst Neurobiol, Dept Pharmacol, Boston, MA 02118 USA
[3] Boston Univ, Ctr Syst Neurobiol, Dept Biomed Engn, Boston, MA 02118 USA
[4] Princeton Univ, Dept Biol Mol, Princeton, NJ 08544 USA
[5] E China Normal Univ, Key Lab Chinese, Minst Educ, Shanghai Inst Brain Funct Genom, Shanghai 200062, Peoples R China
关键词
long-term memory; pharmacogenetic; long-term potentiation; protein knockout;
D O I
10.1073/pnas.0703344104
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Although the functions of alpha-Ca2+/calmodulin-dependent kinase II (CaMKII) have been studied extensively, the role of beta CaMKII, 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 beta CaMKII activity is restricted to the hippocampal dentate gyrus, the region where long-term potentiation was originally discovered. We demonstrate that beta CaMKII 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 beta CaMKII 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 beta CaMKII activity. This study provides evidence not only for the functional role of beta CaMKII 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.
引用
收藏
页码:16317 / 16322
页数:6
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