The molecular mechanisms of spacing effect

间距效应的分子机制

• 批准号: 21500318
• 负责人: MIYASHITA Tomoyuki
• 金额: $ 2.75万
• 依托单位: 財団法人東京都医学総合研究所 (2011)Tokyo Metropolitan Organization for Medical Research (2009-2010)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21500318/
• 关键词: Spacing effect; MAPK; CREB; c-fos; drosophila; memory; Drosophila

Memory formed after spaced training, repeated training with rest intervals between each training, is more stable than memory formed after massed training, repeated training without rest intervals. This "spacing effect" on memory was reported more than 100 yrs ago. However, it is still not clear why rest intervals strengthen memory. In Drosophila, spaced training produces CREB-dependent long-term memory(LTM) whereas, massed training suppresses LTM. Therefore, we examined spacing effect on expressions of CREB and c-fos, an upstream transcription factor of CREB. We found significant increase in expressions of CREB and c-fos during spaced training but not massed training. Transcriptional activity of c-fos is activated by ERK, which is activated by MEK-dependent phosphorylation. We also found significant increase in phosphorylation of ERK during spaced training. Interestingly, however, ERK phosphorylation was increased during each rest intervals and decreased during each training period. MEK inhibitors exclusively impaired LTM formation. These results suggest that rest intervals of spaced training is required for activation of ERK.

间隔训练（每次训练之间有休息间隔的重复训练）形成的记忆比集中训练（没有休息间隔的重复训练）形成的记忆更稳定。一百多年前就报道过这种对记忆的“间隔效应”。然而，目前还不清楚为什么休息时间可以增强记忆力。在果蝇中，间隔训练会产生 CREB ​​依赖性长期记忆 (LTM)，而集中训练会抑制 LTM。因此，我们研究了间隔对CREB和CREB上游转录因子c-fos表达的影响。我们发现在间隔训练期间 CREB ​​和 c-fos 的表达显着增加，但在集中训练期间没有显着增加。 c-fos 的转录活性由 ERK 激活，而 ERK 是由 MEK 依赖性磷酸化激活的。我们还发现间隔训练期间 ERK 磷酸化显着增加。然而有趣的是，ERK 磷酸化在每个休息间隔期间增加，而在每个训练期间减少。 MEK 抑制剂专门损害 LTM 的形成。这些结果表明，间隔训练的休息间隔对于激活 ERK 是必需的。

项目成果

Reactive oxygen species are not involved in the onset of age‐related memory impairment in Drosophila

活性氧与果蝇年龄相关记忆障碍的发生无关

• DOI: 10.1111/j.1601-183x.2011.00748.x
• 发表时间: 2012-02-01
• 期刊: Genes
• 影响因子: 3.5
• 作者: Y. Hirano;Y. Kuriyama;T. Miyashita;J. Horiuchi;M. Saitoe
• 通讯作者: M. Saitoe

Mg2+ Block of Drosophila NMDA Receptors Is Required for Long-Term Memory Formation and CREB-Dependent Gene Expression

果蝇 NMDA 受体的 Mg2 阻断是长期记忆形成和 CREB ​​依赖性基因表达所必需的

• DOI: 10.1016/j.neuron.2012.03.039
• 发表时间: 2012-06-07
• 期刊: Neuron
• 影响因子: 16.2
• 作者: T. Miyashita;Yoshiaki Oda;J. Horiuchi;Jerry C. P. Yin;T. Morimoto;M. Saitoe
• 通讯作者: M. Saitoe

Drosophila PQBP1 regulates learning acquisition at projection neurons in aversive olfactory conditioning

果蝇 PQBP1 调节厌恶嗅觉调节中投射神经元的学习获取

• 发表时间: 2010
• 作者: Tamura T.; Horiuchi D.; Chen YC.; Sone M.; Miyashita T.; Saitoe M.; Yoshimura N.; Chiang AS.; Okazawa H.
• 通讯作者: Okazawa H.

Why rest interval required for long term memory

为什么长期记忆需要休息间隔

• 发表时间: 2009
• 作者: 宮下知之;齊藤実
• 通讯作者: 齊藤実

Why rest intervals are required for long-term memory formation?

为什么长期记忆的形成需要休息时间？

• 发表时间: 2010
• 作者: 宮下知之