Adrenergic Signaling in Synaptic Plasticity and Learning

突触可塑性和学习中的肾上腺素信号传导

基本信息

  • 批准号:
    6873733
  • 负责人:
  • 金额:
    $ 35.11万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2002
  • 资助国家:
    美国
  • 起止时间:
    2002-07-01 至 2006-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): We propose to examine the role of adrenergic signaling in synaptic plasticity, learning and memory using mouse molecular genetics. Specifically, we have created mice that are unable to synthesize norepinephrine (NE) and epinephrine due to a targeted disruption of the dopamine B-hydroxylase (Dbh) gene. Homozygotes (Dbh-/-) completely lack NE; however NE can be restored rapidly in vivo and in vitro using the synthetic amino acid precursor of NE (DOPS). This model has several advantages over prior pharmacologic approaches, including completeness of effect, specificity for NE, and reversibility. Prior studies using various techniques have often generated conflicting results with regard to the roles of NE in synaptic plasticity, learning and memory. Some studies have suggested a role for NE in the formation of emotional (aversive) memories. To test this possibility, we have begun to characterize the ability of Dbh-/- mice to learn and remember an aversive event using fear conditioning. Preliminary results indicate a specific deficit in the consolidation of contextual but not cued memory, suggesting hippocampal function may be altered in the absence of NE. For this reason we have begun to examine synaptic plasticity in the hippocampus. Preliminary results from these studies suggest that the late phase of long-term potentiation in region CAl is deficient. Because other studies have suggested a critical role of synaptic plasticity in region CAl for learning and memory, we propose to examine whether intracellular signaling pathways implicated in learning and memory are altered in region CAl following stimuli that elicit the late phase of LTP in vitro, and following fear conditioning in vivo. Finally, we will test whether compensation for the absence of NE occurs during development, and whether dopamine released from the adrenergic terminals of Dbh-/- mice can substitute at least partially for NE. These goals will be achieved through the use of a second mouse model (Th-/-/Dat-Th+/-) that should lack DA as well as NE in the adrenergic neurons specifically. Some of these mice will be raised with NE present (by supplying L-DOPA pre- and postnatally). L-DOPA will then be withdrawn in half prior to using the mice in the above studies.
描述(由申请人提供):我们建议研究……的作用

项目成果

期刊论文数量(0)
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STEVEN A THOMAS其他文献

STEVEN A THOMAS的其他文献

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{{ truncateString('STEVEN A THOMAS', 18)}}的其他基金

Catecholaminergic Signaling in Normal Cognition, Aging and Models of Alzheimer's Disease
正常认知、衰老和阿尔茨海默病模型中的儿茶酚胺能信号传导
  • 批准号:
    10121456
  • 财政年份:
    2020
  • 资助金额:
    $ 35.11万
  • 项目类别:
Norepinephrine: A Novel Regulator of Amyloid Beta-42 Peptides
去甲肾上腺素:淀粉样蛋白 Beta-42 肽的新型调节剂
  • 批准号:
    9761419
  • 财政年份:
    2018
  • 资助金额:
    $ 35.11万
  • 项目类别:
Molecular Mechanisms of the Stress Response
应激反应的分子机制
  • 批准号:
    8630024
  • 财政年份:
    2014
  • 资助金额:
    $ 35.11万
  • 项目类别:
Molecular Mechanisms of the Stress Response
应激反应的分子机制
  • 批准号:
    9020825
  • 财政年份:
    2014
  • 资助金额:
    $ 35.11万
  • 项目类别:
Inducible recombination and gene expression in specific neurotransmitter systems
特定神经递质系统中的诱导重组和基因表达
  • 批准号:
    8225329
  • 财政年份:
    2008
  • 资助金额:
    $ 35.11万
  • 项目类别:
Inducible recombination and gene expression in specific neurotransmitter systems
特定神经递质系统中的诱导重组和基因表达
  • 批准号:
    8024532
  • 财政年份:
    2008
  • 资助金额:
    $ 35.11万
  • 项目类别:
Inducible recombination and gene expression in specific neurotransmitter systems
特定神经递质系统中的诱导重组和基因表达
  • 批准号:
    7778821
  • 财政年份:
    2008
  • 资助金额:
    $ 35.11万
  • 项目类别:
Inducible recombination and gene expression in specific neurotransmitter systems
特定神经递质系统中的诱导重组和基因表达
  • 批准号:
    7637454
  • 财政年份:
    2008
  • 资助金额:
    $ 35.11万
  • 项目类别:
Inducible neuronal inactivation in mice
诱导小鼠神经元失活
  • 批准号:
    6966850
  • 财政年份:
    2005
  • 资助金额:
    $ 35.11万
  • 项目类别:
Inducible neuronal inactivation in mice
诱导小鼠神经元失活
  • 批准号:
    7140433
  • 财政年份:
    2005
  • 资助金额:
    $ 35.11万
  • 项目类别:
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