Acetylcholine mediates learning-dependent AMPA receptor delivery into the CA3-CA1 synapses

乙酰胆碱介导学习依赖性 AMPA 受体递送至 CA3-CA1 突触

• 批准号: 20590232
• 负责人: MITSUSHIMA Dai
• 金额: $ 3.16万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590232/
• 关键词: 海馬; アセチルコリン; 学習・記憶; AMPA受容体; シナプス移行; GluR1 subunit; ムスカリン受容体; NMDA受容体

By combining in vivo gene delivery with in vitro patch-clamp recordings, we found that hippocampal-dependent inhibitory avoidance (IA) learning drives recombinant GluR1, an AMPA receptor subunit, into synapses formed between CA3 and CA1 pyramidal neurons. Bilateral expression of delivery blocker further revealed that contextual learning requires AMPA receptor delivery in CA1 synapses. Pretreatment of scopolamine, not only impaired the IA learning, but also blocked the AMPA receptor delivery. In paired-recording study, scopolamine pretreatment successfully blocked the effect of mutated fragment of GluR1 cytoplasmic tail (GFP-MPR-DD), a construct inhibits learning-dependent synaptic delivery of AMPA receptors. Conversely, expression of control fragment (GFP-MPR-AA) did not affect the learning-dependent delivery. Further, extracellular acetylcholine level at CA1 region significantly increased during and after IA learning for 60 min. Control animals (such as naive, shock only, or walk through rats) did not show the increase. These results suggest that cholinergic activation is required for learning-dependent AMPA receptor delivery into the CA3-CA1 synapses.

通过将体内基因传递与体外膜片钳记录相结合，我们发现，海马依赖性抑制性回避（IA）学习驱动重组GluR 1（AMPA受体亚基）进入CA 3和CA 1锥体神经元之间形成的突触。传递阻滞剂的双侧表达进一步揭示了情境学习需要CA 1突触中的AMPA受体传递。东莨菪碱预处理不仅损害了IA学习，而且阻断了AMPA受体的传递。在配对记录研究中，东莨菪碱预处理成功地阻断了突变的GluR 1胞质尾片段（GFP-MPR-DD）的作用，该结构抑制了AMPA受体的学习依赖性突触传递。相反，对照片段（GFP-MPR-AA）的表达不影响学习依赖性递送。此外，细胞外乙酰胆碱水平在CA 1区显着增加期间和IA学习后60分钟。对照动物（如幼稚，休克，或步行通过大鼠）没有显示出增加。这些结果表明，胆碱能激活所需的学习依赖性AMPA受体传递到CA 3-CA 1突触。

项目成果

The Caenorhabditis elegans Elongator complex regulates neuronal alpha-tubulin acetylation.

• DOI: 10.1371/journal.pgen.1000820
• 发表时间: 2010-01-22
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Solinger JA;Paolinelli R;Klöss H;Scorza FB;Marchesi S;Sauder U;Mitsushima D;Capuani F;Stürzenbaum SR;Cassata G
• 通讯作者: Cassata G

自由行動ラットにおける海馬学習のメカニズム:アセチルコリンによるAMPA受容体のシナプス移行

自由活动大鼠海马学习机制：乙酰胆碱对 AMPA 受体的突触易位

• 发表时间: 2008
• 作者: 森本恵子;他;美津島大
• 通讯作者: 美津島大

Food Availability Affects Orexin A/ Hypocretin-1-Induced Inhibition of Pulsatile Luteinizing Hormone Secretion in Female Rats

食物供应量影响食欲素 A/Hypocretin-1 诱导的雌性大鼠脉动黄体激素分泌抑制

• DOI: 10.1159/000257408
• 发表时间: 2009
• 期刊: Neuroendocrinology
• 影响因子: 4.1
• 作者: Miyako Furuta;D. Mitsushima;K. Shinohara;F. Kimura;T. Funabashi
• 通讯作者: T. Funabashi

Changes in neurotransmitter levels and proinflammatory cytokine mRNA expressions in the mice olfactory bulb following nanoparticle exposure

• DOI: 10.1016/j.taap.2007.09.009
• 发表时间: 2008-01-15
• 期刊: TOXICOLOGY AND APPLIED PHARMACOLOGY
• 影响因子: 3.8
• 作者: Tin-Tin-Win-Shwe;Mitsushima, Dai;Fujimaki, Hidekazu
• 通讯作者: Fujimaki, Hidekazu

Social isolation produces glucocorticoid-mediated disruption of cortical circuit formation.

社会隔离会导致糖皮质激素介导的皮质回路形成破坏。

• 发表时间: 2009
• 作者: Miyazaki T;Takase K;Tada H;Mitsushima D;Takahashi T.
• 通讯作者: Takahashi T.