Translation Regulation in Hippocampal LTP and LTD

海马 LTP 和 LTD 的翻译调节

基本信息

  • 批准号:
    7455113
  • 负责人:
  • 金额:
    $ 39.33万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2005
  • 资助国家:
    美国
  • 起止时间:
    2005-07-01 至 2009-07-14
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): This proposal is designed to investigate the biochemical signaling mechanisms underlying metabotropic glutamate receptor-dependent (mGluR) long-term depression (LTD) and late-phase long-term potentiation (L-LTP) in area CA1 of the mouse hippocampus. These forms of synaptic plasticity previously have been shown to be dependent on new protein synthesis. However, virtually nothing is known about the signaling cascades that couple either mGluRs or N-methyl-D-aspartate (NMDA) receptors to the protein translation machinery during these forms of plasticity. If both mGluR-LTD and L-LTP are both dependent on protein synthesis, then several critical questions arise. Are the same signaling pathways required to couple mGluRs and NMDA receptors to the translation machinery during mGluR-LTD and L-LTP, respectively? Are there mRNAs that are preferentially translated during mGluR-LTD versus L-LTP? Using a combination of biochemical, immunocytochemical, pharmacological, and electrophysiological techniques, as well as genetically-modified mice, we propose to 1) test the hypothesis that cap-dependent translation signaling pathways are involved in mGluR-dependent LTD and late-phase LTP, 2) test the hypothesis that S6-directed translation signaling pathways are involved in mGluR-dependent LTD and late-phase LTP, and 3) test the hypothesis that fragile X mental retardation protein is involved in the regulation of mGluR-dependent LTD but not late-phase LTP, and that translation is regulated improperly during mGluR-dependent LTD in mouse models of fragile X mental retardation. These studies should provide insights into the signaling cascades that couple mGluRs and NMDA receptors to protein translation forms of synaptic plasticity that may be important for learning and memory. These studies may also elucidate unique signaling cascades in the hippocampus that will be critical for understanding the behavioral abnormalities and memory impairments associated with fragile X mental retardation.
描述(由申请人提供):本提案旨在研究小鼠海马CA 1区代谢型谷氨酸受体依赖性(mGluR)长时程抑制(LTD)和晚期长时程增强(L-LTP)的生化信号传导机制。这些形式的突触可塑性先前已被证明是依赖于新的蛋白质合成。然而,几乎没有什么是已知的信号级联耦合mGluRs或N-甲基-D-天冬氨酸(NMDA)受体的蛋白质翻译机制在这些形式的可塑性。如果mGluR-LTD和L-LTP都依赖于蛋白质合成,那么就会出现几个关键问题。在mGluR-LTD和L-LTP期间,将mGluRs和NMDA受体分别偶联到翻译机制所需的信号通路是否相同?在mGluR-LTD和L-LTP中是否存在优先翻译的mRNA?使用生物化学、免疫细胞化学、药理学和电生理学技术的组合,以及基因修饰小鼠,我们提出1)检验帽依赖性翻译信号通路参与mGluR依赖性LTD和晚期LTP的假设,2)检验S6定向翻译信号通路参与mGluR依赖性LTD和晚期LTP的假设,(3)在脆性X智力低下小鼠模型中,验证脆性X智力低下蛋白参与mGluR依赖性LTD的调节,而不参与LTP晚期的调节,以及在mGluR依赖性LTD过程中翻译调节不当的假设。这些研究应该提供的信号级联耦合mGluRs和NMDA受体的突触可塑性,可能是重要的学习和记忆的蛋白质翻译形式的见解。这些研究还可能阐明海马体中独特的信号级联,这对于理解与脆性X智力低下相关的行为异常和记忆障碍至关重要。

项目成果

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Eric Klann其他文献

Eric Klann的其他文献

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{{ truncateString('Eric Klann', 18)}}的其他基金

Dysregulated Ribosomal Protein Synthesis in Amyloid and Tau Mouse Models
淀粉样蛋白和 Tau 小鼠模型中核糖体蛋白合成失调
  • 批准号:
    10201329
  • 财政年份:
    2021
  • 资助金额:
    $ 39.33万
  • 项目类别:
Translational Control in Memory and Brain Disorders
记忆和大脑疾病的翻译控制
  • 批准号:
    10399633
  • 财政年份:
    2021
  • 资助金额:
    $ 39.33万
  • 项目类别:
Translational Control in Memory and Brain Disorders
记忆和大脑疾病的翻译控制
  • 批准号:
    10613505
  • 财政年份:
    2021
  • 资助金额:
    $ 39.33万
  • 项目类别:
Translational Control in Memory and Brain Disorders
记忆和大脑疾病的翻译控制
  • 批准号:
    10239794
  • 财政年份:
    2021
  • 资助金额:
    $ 39.33万
  • 项目类别:
Molecular and Cellular Cognition Meeting
分子和细胞认知会议
  • 批准号:
    8705563
  • 财政年份:
    2013
  • 资助金额:
    $ 39.33万
  • 项目类别:
Molecular and Cellular Cognition Meeting
分子和细胞认知会议
  • 批准号:
    8597494
  • 财政年份:
    2013
  • 资助金额:
    $ 39.33万
  • 项目类别:
Molecular and Cellular Cognition Meeting
分子和细胞认知会议
  • 批准号:
    8912913
  • 财政年份:
    2013
  • 资助金额:
    $ 39.33万
  • 项目类别:
Training Program in Neuroscience
神经科学培训计划
  • 批准号:
    8720873
  • 财政年份:
    2013
  • 资助金额:
    $ 39.33万
  • 项目类别:
Targeting Mitochondrial Superoxide in Angelman Syndrome
靶向天使综合征中的线粒体超氧化物
  • 批准号:
    8337857
  • 财政年份:
    2011
  • 资助金额:
    $ 39.33万
  • 项目类别:
Targeting Mitochondrial Superoxide in Angelman Syndrome
靶向天使综合征中的线粒体超氧化物
  • 批准号:
    8289784
  • 财政年份:
    2011
  • 资助金额:
    $ 39.33万
  • 项目类别:

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