2003 Fiscal Year Final Research Report Summary
Molecular mechanisms of cognitive memory formation in the primate
| Project/Area Number |
13680895
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
神経・脳内生理学
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TOKUYAMA Wataru The University of Tokyo, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (70323615)
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| Project Period (FY) |
2001 – 2003
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| Keywords | Long-term memory / Primates / BDNF / IEG |
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| Research Abstract |
In this research project, I aimed to elucidate molecular mechanisms of long-term memory formation in the primate using Japanese macaque monkeys (Macaca fuscata). Monkeys were trained to perform a visual pair-association (PA) task that was used to assess declarative memory formation in the human. Luring learning of new associations, I examined up-regulation of mRNA expression levels using a quantitative RPPCR and in situ hybridization methods. I reported that an expression level of mRNA for brain-derived neumtrophic factor (BDNF) was significantly up-regulated in the inferior temporal cortex In addition, I found that the expression of the mRNA of an immediate-early gene (IEG), zif268, was up-regulated selectively in the inferior temporal cortex during the formation of PA memory (Tokuyama et al. Journal of Neurochemistry, 2002). I have also examined whether the expression levels of other plasticity related genes were up-regulated during PA memory formation.
To investigate functional roles of BDNF and zif268 genes in the formation and maintenance of long-term memory, I planed to inject antisense oligonucleotide into the monkey inferior temporal cortex to inhibit expressions of these genes. I prepared two split-brain monkeys by surgically transecting the commissural fibers and trained them to perform the PA task. I isolated the BDNF gene of the Japanese monkey and sequenced. Based on the sequence, antisense and control mismatch oligonucleotides were designed. I developed in vivo experimental model to test the effects of the BDNF antisense oligonucleotide. I found that apoptotic cell death was induced in mitral and granule cells of the adult rat olfactory bulb after the lateral olfactory tract transection. Using this experimental model, I have examined the effects of BDNF antisense oligonucleotide on cell survival and death in vivo.
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Research Products
(18 results)
