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学科主题: 精神卫生
题名:
Delayed Noradrenergic Activation in the Dorsal Hippocampus Promotes the Long-Term Persistence of Extinguished Fear
作者: Chai, Ning1,2,3,4; Liu, Jian-Feng1,2,5; Xue, Yan-Xue5; Yang, Chang6,7; Yan, Wei1,2,5; Wang, Hui-Min1,2,5; Luo, Yi-Xiao1,2,5; Shi, Hai-Shui8; Wang, Ji-Shi6,7; Bao, Yan-Ping5; Meng, Shi-Qiu1,2,5; Ding, Zeng-Bo5; Wang, Xue-Yi3,4; Lu, Lin1,2,5,9,10
刊名: NEUROPSYCHOPHARMACOLOGY
发表日期: 2014-07-01
DOI: 10.1038/npp.2014.42
卷: 39, 期:8, 页:1933-1945
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Neurosciences ; Pharmacology & Pharmacy ; Psychiatry
研究领域[WOS]: Neurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry
关键词[WOS]: REQUIRES PROTEIN-SYNTHESIS ; KINASE ANCHORING PROTEINS ; NUCLEUS-ACCUMBENS CORE ; CONDITIONED FEAR ; MEMORY CONSOLIDATION ; BASOLATERAL AMYGDALA ; CONTEXTUAL FEAR ; SIGNALING PATHWAY ; PREFRONTAL CORTEX ; D-CYCLOSERINE
英文摘要:

Fear extinction has been extensively studied, but little is known about the molecular processes that underlie the persistence of extinction long-term memory (LTM). We found that microinfusion of norepinephrine (NE) into the CAI area of the dorsal hippocampus during the early phase (0 h) after extinction enhanced extinction LTM at 2 and 14 days after extinction. lntra-CA I infusion of NE during the late phase (12 h) after extinction selectively promoted extinction LTM at 14 days after extinction that was blocked by the beta-receptor antagonist propranolol, protein kinase A (PKA) inhibitor Rp-cAMPS, and protein synthesis inhibitors anisomycin and emetine. The phosphorylation levels of PKA, cyclic adenosine monophosphate response element-binding protein (CREB), GluR I, and the membrane GluRI level were increased by NE during the late phase after extinction that was also blocked by propranolol and Rp-cAMPS. These results suggest that the enhancement of extinction LTM persistence induced by NE requires the activation of the)beta-receptor/PKA/CREB signaling pathway and membrane GluR I trafficking. Moreover, extinction increased the phosphorylation levels of Erk1/2, CREB, and GluR I, and the membrane GluR I level during the late phase, and anisomycin/emetine alone disrupted the persistence of extinction LTM, indicating that the persistence of extinction LTM requires late-phase protein synthesis in the CA I. Propranolol and Rp-cAMPS did not completely disrupt the persistence of extinction LTM, suggesting that another)beta-receptor/PKA-independent mechanism underlies the persistence of extinction LTM. Altogether, our results showed that enhancing hippocampal noradrenergic activity during the late phase after extinction selectively promotes the persistence of extinction LTM.

语种: 英语
所属项目编号: 81271489 ; 31230033 ; 81221002
项目资助者: Natural Science Foundation of China
WOS记录号: WOS:000337550600015
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63793
Appears in Collections:北京大学精神卫生研究所_期刊论文

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作者单位: 1.Peking Univ, Inst Mental Hlth, Hosp 6, Beijing 100191, Peoples R China
2.Peking Univ, Key Lab Mental Hlth, Hosp 6, Minist Hlth, Beijing 100191, Peoples R China
3.Hebei Med Univ, Inst Mental Hlth, Shijiazhuang 050031, Peoples R China
4.Hebei Med Univ, Hebei Brain Ageing & Cognit Neurosci Lab, Shijiazhuang 050031, Peoples R China
5.Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
6.Guiyang Med Univ, Affiliated Hosp, Guiyang, Peoples R China
7.Guiyang Med Univ, Sch Pharm, Guiyang, Peoples R China
8.Hebei Med Univ, Dept Biochem & Mol Biol, Basic Med Coll, Shijiazhuang 050031, Peoples R China
9.Peking Univ, PekingTsinghua Ctr Life Sci, Beijing 100191, Peoples R China
10.Peking Univ, PKU IDG McGovem Inst Brain Res, Beijing 100191, Peoples R China

Recommended Citation:
Chai, Ning,Liu, Jian-Feng,Xue, Yan-Xue,et al. Delayed Noradrenergic Activation in the Dorsal Hippocampus Promotes the Long-Term Persistence of Extinguished Fear[J]. NEUROPSYCHOPHARMACOLOGY,2014,39(8):1933-1945.
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