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
- 来源:
- 关键词:
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 L-DOPA will then be withdrawn in half prior to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:
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: