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Delayed Noradrenergic Activation in the Dorsal Hippocampus Promotes the Long-Term Persistence of Extinguished Fear
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
2014-07-01
DOI10.1038/npp.2014.42
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
资助者Natural Science Foundation of China ; Natural Science Foundation of China
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
资助者Natural Science Foundation of China ; Natural Science Foundation of China
WOS记录号WOS:000337550600015
引用统计
被引频次:17[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63793
专题北京大学精神卫生研究所
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
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GB/T 7714
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.
APA Chai, Ning.,Liu, Jian-Feng.,Xue, Yan-Xue.,Yang, Chang.,Yan, Wei.,...&Lu, Lin.(2014).Delayed Noradrenergic Activation in the Dorsal Hippocampus Promotes the Long-Term Persistence of Extinguished Fear.NEUROPSYCHOPHARMACOLOGY,39(8),1933-1945.
MLA Chai, Ning,et al."Delayed Noradrenergic Activation in the Dorsal Hippocampus Promotes the Long-Term Persistence of Extinguished Fear".NEUROPSYCHOPHARMACOLOGY 39.8(2014):1933-1945.
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