Cholinergic modulation of IEG expression

IEG 表达的胆碱能调节

• 批准号: 6791745
• 负责人: ANN E POWER
• 金额: $ 4.89万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-05 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6791745
• 关键词: acetylcholine; amygdala; behavioral /social science research tag; brain mapping; gene expression; hippocampus; laboratory rat; long term memory; mitogen activated protein kinase; molecular psychobiology; muscarinic receptor; negative reinforcements; neocortex; neural plasticity; postdoctoral investigator; prosencephalon; receptor expression; regulatory gene

DESCRIPTION (provided by applicant): Muscarinic cholinergic receptor (mR) activation has robust effects on long-term memory storage, physiological plasticity and can induce immediate early gene (lEG) expression. This study will investigate the relationship between mR effects on memory and lEG expression. Rats will be trained in an inhibitory avoidance paradigm. Avoidance of the shock-associated compartment will be the major index of retention. Some rats will be sacrificed after training to allow analysis of effects of memory enhancing posttraining mR agonism on mRNA induction of the lEGs EGR-1, c-fos and Arc and the phosphorylation of ERK1/2 during memory consolidation. Experiment I will include broad analysis of systemic post-training mR effects, including effects in neocortex, hippocampus and amygdala. Experiment II will employ temporary inactivation of major cholinergic basal forebrain regions after training to investigate the contributions of endogenous cholinergic release during consolidation to long-term memory, lEG expression and ERK1/2 activation. Experiment III will investigate which signaling cascades (e.g., protein kinases) are involved in effects of mR activation on memory and immediate early gene expression.

描述（由申请人提供）：毒蕈碱胆碱能受体（MR）激活对长期记忆存储，生理可塑性具有强大的影响，并且可以诱导立即的早期基因（腿）表达。这项研究将研究MR对记忆的影响与腿部表达之间的关系。大鼠将接受抑制性回避范式的训练。避免与冲击相关的隔室将是保留的主要指数。在训练后将牺牲一些大鼠，以允许分析记忆的影响，从而增强训练后的MR激动剂对腿部EGR-1，​​C-FOS和ARC的mRNA诱导以及在记忆巩固过程中ERK1/2的磷酸化。实验I将包括对系统性训练后MR效应的广泛分析，包括新皮层，海马和杏仁核的影响。实验II将在训练后暂时灭活胆碱能基础前脑区域，以研究内源性胆碱能释放在整合过程中对长期记忆，腿部表达和ERK1/2激活的贡献。实验III将研究哪些信号级联反应（例如蛋白激酶）参与MR激活对记忆和直接早期基因表达的影响。