• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Selective pharmacogenetic inhibition of mammalian target of Rapamycin complex I (mTORC1) blocks long-term synaptic plasticity and memory storage
【24h】

Selective pharmacogenetic inhibition of mammalian target of Rapamycin complex I (mTORC1) blocks long-term synaptic plasticity and memory storage

机译：雷帕霉素复合物I（mTORC1）对哺乳动物靶标的选择性药理抑制作用可阻止长期突触可塑性和记忆存储

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Both the formation of long-term memory (LTM) and late-long-term potentiation (L-LTP), which is thought to represent the cellular model of learning and memory, require de novo protein synthesis. The mammalian target of Rapamycin (mTOR) complex I (mTORC1) integrates information from various synaptic inputs and its best characterized function is the regulation of translation. Although initial studies have shown that rapamycin reduces L-LTP and partially blocks LTM, recent genetic and pharmacological evidence indicating that mTORC1 promotes L-LTP and LTM is controversial. Thus, the role of mTORC1 in L-LTP and LTM is unclear. To selectively inhibit mTORC1 activity in the adult brain, we used a "pharmacogenetic" approach that relies on the synergistic action of a drug (rapamycin) and a genetic manipulation (mTOR heterozygotes, mTOR~(+/-) mice) on the same target (mTORC1). Although L-LTP and LTM are normal in mTOR~(+/-) mice, application of a low concentration of rapamycin-one that is subthreshold for WT mice-prevented L-LTP and LTM only in mTOR~(+/-) mice. Furthermore, we found that mTORC1-mediated translational control is required for memory reconsolida-tion. We provide here direct genetic evidence supporting the role of mTORC1 in L-LTP and behavioral memory.
机译：长期记忆（LTM）和晚期长期增强（L-LTP）的形成都被认为代表了学习和记忆的细胞模型，它们都需要从头合成蛋白质。雷帕霉素（mTOR）复合体I（mTORC1）的哺乳动物靶标整合了来自各种突触输入的信息，其最佳表征的功能是翻译调控。尽管初步研究表明雷帕霉素可降低L-LTP并部分阻断LTM，但最近的遗传和药理学证据表明mTORC1可以促进L-LTP，而LTM仍存在争议。因此，尚不清楚mTORC1在L-LTP和LTM中的作用。为了选择性抑制成年大脑中的mTORC1活性，我们使用了“药物遗传”方法，该方法依赖于药物（雷帕霉素）和基因操作（mTOR杂合子，mTOR〜（+/-）小鼠）对同一靶标的协同作用（mTORC1）。尽管L-LTP和LTM在mTOR〜（+/-）小鼠中是正常的，但对WT小鼠亚阈值的低浓度雷帕霉素一的应用仅在mTOR〜（+/-）小鼠中阻止了L-LTP和LTM。 。此外，我们发现记忆重组需要mTORC1介导的翻译控制。我们在这里提供直接的遗传学证据，支持mTORC1在L-LTP和行为记忆中的作用。

著录项

  • 来源
  • 作者

    Loredana Stoica; Ping Jun Zhu; Wei Huang; Hongyi Zhou; Sara C. Kozma; Mauro Costa-Mattioli;

  • 作者单位

    Departments of Neuroscience, Center for Addiction, Learning and Memory (CALM), Baylor College of Medicine, Houston, TX 77030 Departments of Molecular and Cellular Biology, Center for Addiction, Learning and Memory (CALM), Baylor College of Medicine, Houston, TX 77030;

    Departments of Neuroscience, Center for Addiction, Learning and Memory (CALM), Baylor College of Medicine, Houston, TX 77030;

    Departments of Neuroscience, Center for Addiction, Learning and Memory (CALM), Baylor College of Medicine, Houston, TX 77030;

    Departments of Neuroscience, Center for Addiction, Learning and Memory (CALM), Baylor College of Medicine, Houston, TX 77030;

    Department of Cancer and Cell Biology, Metabolic Diseases Institute, College of Medicine, University of Cincinnati, Cincinnati, OH 45237;

    Departments of Neuroscience, Center for Addiction, Learning and Memory (CALM), Baylor College of Medicine, Houston, TX 77030 Departments of Molecular and Cellular Biology, Center for Addiction, Learning and Memory (CALM), Baylor College of Medicine, Houston, TX 77030;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    behavioral learning; pharmacology; fear conditioning;

    机译：行为学习;药理;恐惧条件;

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号