Molecular mechanisms of cognitive memory formation in the primate

灵长类动物认知记忆形成的分子机制

基本信息

批准号：
13680895
负责人：
TOKUYAMA Wataru
金额：
$ 2.62万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680895/
关键词：
Long-term memory Primates BDNF IEG long-term memory primate zif268

项目摘要

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.

在这个研究项目中，我旨在使用日本猕猴（Macaca Fuscata）阐明灵长类动物中长期记忆形成的分子机制。对猴子进行了训练，可以执行视觉成对关联（PA）任务，该任务用于评估人类声明性记忆的形成。我使用定量RPPCR和原位杂交方法来研究新关联的学习，研究了mRNA表达水平的上调。我报道说，在下颞皮层中，明显上调了脑源性肿瘤因子（BDNF）的mRNA表达水平，此外，我发现在pa seemerem（ke kuy to ne Morama）中，在下层临时皮层中选择性地上调了直接依恋基因（IEG），ZIF268，ZIF268，ZIF268的表达。我还研究了在PA记忆形成过程中是否上调了其他相关基因的表达水平。为了研究BDNF和ZIF268基因在长期记忆形成和维持中的功能作用，我计划将反义寡核苷酸注射到猴子下部的临时皮质中，以抑制这些基因的表达。我通过外科手术骨外纤维并训练它们执行PA任务，从而准备了两只分裂的猴子。我隔离了日本猴子的BDNF基因并测序。基于序列，设计了反义和对照不匹配的寡核苷酸。我开发了体内实验模型，以测试BDNF反义寡核苷酸的作用。我发现在侧向嗅球横断后，成年大鼠嗅球的二尖瓣和颗粒细胞中诱导了凋亡细胞死亡。使用此实验模型，我研究了BDNF反义寡核苷酸对体内细胞存活和死亡的影响。