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Learning and Long-term Memory

開催日 2014/9/13
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Remote memory deficit in three strains of mutant mice with immature dentate gyrus phenotype

  • P3-221
  • 昌子 浩孝 / Hirotaka Shoji:1,2 高木 豪 / Tsuyoshi Takagi:3,4 石井 俊輔 / Shunsuke Ishii:4 Graef Isabella A / Isabella A Graef:5 Crabtree Gerald R / Gerald R Crabtree:5 Frankland Paul W / Paul W Frankland:6,7 宮川 剛 / Tsuyoshi Miyakawa:1,2,8 
  • 1:藤田保健衛生大学 / Div Sys Med Sci, ICMS, Fujita Health Univ, Toyoake, Japan 2:CREST, JST / CREST, JST, Saitama, Japan 3:愛知県心身障害者コロニー発達障害研究所 / Dept Perinatol, Inst Dev Res, Aichi, Japan 4:理研 / Lab Mol Genet, RIKEN, Ibaraki, Japan 5:スタンフォード大 / Dept Pathol, Stanford Univ Sch Med, Stanford, USA 6:トロント小児病院 / Hosp Sick Child, Toronto, Canada 7:トロント大 / Dept Physiol, Toronto Univ, Toronto, Canada 8:生理研・行動様式解析室 / Ctr Gene Anal Behav, NIPS, Okazaki, Japan 

The hippocampal dentate gyrus (DG) is considered to play a crucial role in memory processes. To date, we have performed behavioral analyses of more than 160 groups of genetically engineered mice and found that several strains of the mutant mice, such as α-CaMKII heterozygous knockout (KO), forebrain specific calcineurin (CN) KO, and schnurri-2 (Shn-2) KO mice, exhibit similar behavioral abnormalities related to psychiatric disorders such as schizophrenia and bipolar disorder. In those mouse models of psychiatric disorders, adult mutants were found to have 'immature dentate gyrus (iDG)' phenotype, in which almost all the neurons in the DG stay at a pseudo-immature state. Additionally, our previous studies showed that chronic administrations of fluoxetine, a selective serotonin reuptake inhibitor, reverse the established mature state of neurons in the adult DG. Recent study reported that manipulations for increasing new immature neurons in the DG induce remote memory deficit (Akers et al., Science, 2014). However, it remains unknown whether the pseudo-immature state of the DG neurons in those mutant mice lead to remote memory impairment. In this study, we investigated remote memory in those mice with iDG phenotype in the Barnes maze test. At one day after training, α-CaMKII heterozygous KO, CN KO, and Shn-2 KO mice showed no significant difference in time spent around target hole compared with their control mice. However, at approximately 30 days after training, the three strains of mutant mice showed less time spent around target hole than control mice, indicating that the mutants exhibited normal recent memory but impaired remote memory in the Barnes maze test. These results suggest that immature state of the DG neurons is associated with deficits in remote memory in mice.

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