Ca2+ Stimulated Adenylyl Cyclases and Neuroplasticity

Ca2 刺激的腺苷酸环化酶和神经可塑性

基本信息

  • 批准号:
    7192401
  • 负责人:
  • 金额:
    $ 33.24万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1984
  • 资助国家:
    美国
  • 起止时间:
    1984-04-01 至 2009-02-28
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): There is considerable interest in the cellular and molecular basis of memory formation. Studies of learning and memory are of fundamental importance for a better understanding of cognitive disorders in humans including Alzheimer's, autism, aging-related memory loss, and various types of mental retardation. It is the general hypothesis of this proposal that Ca2+ stimulation of the CREB/CRE (cAMP response element)-transcriptional pathway plays a pivotal role in long-lasting, long-term potentiation (L-LTP) and some forms of hippocampus-dependent long-term memory (LTM). Our long-term objectives are to define the mechanisms for Ca2+ stimulation of CRE-mediated transcription in hippocampal neurons and to understand why activation of this pathway is important for LTM and L-LTP. We hypothesize that Ca2+ activation of CRE-mediated transcription requires coactivation of the Erk/MAPK and camp signal transduction pathways. We propose that the critical cAMP signal increase originates from activation of calmodulin-stimulated adenylyl cyclases. We hypothesize that cAMP signaling is required for the nuclear translocation of Erk/MAPK and may also contribute to Ca2+ activation of Erk/MAPK. We also propose that proteolytic degradation of SCOP, a Ras inhibitor, may contribute to Ca2+ activation and sensitization of the Erk/MAPK signal transduction pathway. We hypothesize that long-lasting increases in CRE-mediated transcription, or transcriptional oscillations, in the hippocampus may be due to increased expression of gene products that function as positive-feedback regulators of the Erk/MAPK/CRE transcriptional pathway.
描述(申请人提供):对记忆形成的细胞和分子基础有相当大的兴趣。对学习和记忆的研究对于更好地了解人类的认知障碍,包括阿尔茨海默氏症、自闭症、与衰老相关的记忆丧失和各种类型的精神发育迟缓具有重要的意义。这一假设的基本假设是,钙离子刺激CREB/CRE(cAMP反应元件)转录通路在长时程增强(L-LTP)和某些形式的海马区依赖的长时程记忆(LTM)中起着关键作用。我们的长期目标是明确钙离子刺激Cre介导的海马神经元转录的机制,并了解为什么这一途径的激活对LTM和L LTP具有重要意义。我们推测,钙激活Cre介导的转录需要ERK/MAPK和cAMP信号转导通路的共同激活。我们认为,关键的cAMP信号增加起源于钙调素刺激的腺酰环化酶的激活。我们推测,cAMP信号是ERK/MAPK核转位所必需的,也可能参与了ERK/MAPK的钙激活。我们还认为,Ras抑制剂SCOP的蛋白降解可能有助于激活和敏化Erk/MAPK信号转导通路。我们假设,海马区Cre介导的转录或转录振荡的长期增加可能是由于作为Erk/MAPK/Cre转录途径的正反馈调节因子的基因产物表达增加所致。

项目成果

期刊论文数量(0)
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科研奖励数量(0)
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DANIEL R STORM其他文献

DANIEL R STORM的其他文献

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{{ truncateString('DANIEL R STORM', 18)}}的其他基金

Role of PI3 Kinase and MAP Kinase in Memory Retrieval
PI3 激酶和 MAP 激酶在记忆检索中的作用
  • 批准号:
    7620032
  • 财政年份:
    2008
  • 资助金额:
    $ 33.24万
  • 项目类别:
Role of PI3 Kinase and MAP Kinase in Memory Retrieval
PI3 激酶和 MAP 激酶在记忆检索中的作用
  • 批准号:
    8037101
  • 财政年份:
    2008
  • 资助金额:
    $ 33.24万
  • 项目类别:
Role of PI3 Kinase and MAP Kinase in Memory Retrieval
PI3 激酶和 MAP 激酶在记忆检索中的作用
  • 批准号:
    8240050
  • 财政年份:
    2008
  • 资助金额:
    $ 33.24万
  • 项目类别:
Role of PI3 Kinase and MAP Kinase in Memory Retrieval
PI3 激酶和 MAP 激酶在记忆检索中的作用
  • 批准号:
    7522246
  • 财政年份:
    2008
  • 资助金额:
    $ 33.24万
  • 项目类别:
Role of PI3 Kinase and MAP Kinase in Memory Retrieval
PI3 激酶和 MAP 激酶在记忆检索中的作用
  • 批准号:
    7795683
  • 财政年份:
    2008
  • 资助金额:
    $ 33.24万
  • 项目类别:
Memory Enhancement by A Genetic Increase in cAMP Signals
通过 cAMP 信号的遗传增强增强记忆
  • 批准号:
    7048100
  • 财政年份:
    2006
  • 资助金额:
    $ 33.24万
  • 项目类别:
Memory Enhancement by a Genetic Increase in cAMP Signals
cAMP 信号基因增加可增强记忆
  • 批准号:
    8786106
  • 财政年份:
    2006
  • 资助金额:
    $ 33.24万
  • 项目类别:
Memory Enhancement by A Genetic Increase in cAMP Signals
通过 cAMP 信号的遗传增强增强记忆
  • 批准号:
    7764779
  • 财政年份:
    2006
  • 资助金额:
    $ 33.24万
  • 项目类别:
Memory Enhancement by A Genetic Increase in cAMP Signals
通过 cAMP 信号的遗传增强增强记忆
  • 批准号:
    7579802
  • 财政年份:
    2006
  • 资助金额:
    $ 33.24万
  • 项目类别:
Memory Enhancement by a Genetic Increase in cAMP Signals
cAMP 信号基因增加可增强记忆
  • 批准号:
    8401162
  • 财政年份:
    2006
  • 资助金额:
    $ 33.24万
  • 项目类别:

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