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Role of Hippocampal beta-Adrenergic and Glucocorticoid Receptors in the Novelty-Induced Enhancement of Fear Extinction
Liu, Jian-Feng1,2,3; Yang, Chang1,2; Deng, Jia-Hui1,2,3; Yan, Wei1,2,3; Wang, Hui-Min1,2,3; Luo, Yi-Xiao1,2,3; Shi, Hai-Shui6; Meng, Shi-Qiu1,2,3; Chai, Bai-Sheng4,5,7; Fang, Qin4,5; Chai, Ning7,8; Xue, Yan-Xue3; Sun, Jia4,5; Chen, Chen1,2,3; Wang, Xue-Yi7,8; Wang, Ji-Shi4,5; Lu, Lin1,2,3,9,10
关键词beta-adrenergic receptors behavioral tag extinction glucocorticoid receptors hippocampus
刊名JOURNAL OF NEUROSCIENCE
2015-05-27
DOI10.1523/JNEUROSCI.0005-15.2015
35期:21页:8308-8321
收录类别SCI ; SSCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences
资助者National Basic Research Program of China ; Natural Science Foundation of China ; National Basic Research Program of China ; Natural Science Foundation of China
研究领域[WOS]Neurosciences & Neurology
关键词[WOS]LONG-TERM POTENTIATION ; RAT DENTATE GYRUS ; REQUIRES PROTEIN-SYNTHESIS ; ONE-TRIAL AVOIDANCE ; MEMORY CONSOLIDATION ; NORADRENERGIC ACTIVATION ; BASOLATERAL AMYGDALA ; NEUROTROPHIC FACTOR ; CONDITIONED FEAR ; SPATIAL NOVELTY
英文摘要

Fear extinction forms a new memory but does not erase the original fear memory. Exposure to novelty facilitates transfer of short-term extinction memory to long-lasting memory. However, the underlying cellular and molecular mechanisms are still unclear. Using a classical contextual fear-conditioning model, we investigated the effect of novelty on long-lasting extinction memory in rats. We found that exposure to a novel environment but not familiar environment 1 h before or after extinction enhanced extinction long-term memory (LTM) and reduced fear reinstatement. However, exploring novelty 6 h before or after extinction had no such effect. Infusion of the beta-adrenergic receptor (beta AR) inhibitor propranolol and glucocorticoid receptor (GR) inhibitor RU486 into the CA1 area of the dorsal hippocampus before novelty exposure blocked the effect of novelty on extinction memory. Propranolol prevented activation of the hippocampal PKA-CREB pathway, and RU486 prevented activation of the hippocampal extracellular signal-regulated kinase 1/2 (Erk1/2)-CREB pathway induced by novelty exposure. These results indicate that the hippocampal beta AR-PKA-CREB and GR-Erk1/2-CREB pathways mediate the extinction-enhancing effect of novelty exposure. Infusion of RU486 or the Erk1/2 inhibitor U0126, but not propranolol or the PKA inhibitor Rp-cAMPS, into the CA1 before extinction disrupted the formation of extinction LTM, suggesting that hippocampal GR and Erk1/2 but not beta AR or PKA play critical roles in this process. These results indicate that novelty promotes extinction memory via hippocampal beta AR- and GR-dependent pathways, and Erk1/2 may serve as a behavioral tag of extinction.

语种英语
所属项目编号2015CB856400 ; 2015CB553503 ; 31230033 ; 91432303 ; 81221002
资助者National Basic Research Program of China ; Natural Science Foundation of China ; National Basic Research Program of China ; Natural Science Foundation of China
WOS记录号WOS:000356673100023
Citation statistics
Cited Times:6[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64798
Collection北京大学精神卫生研究所
作者单位1.Guiyang Med Univ, Sch Pharm, Guiyang 550004, Peoples R China
2.Peking Univ, Inst Mental Hlth, Hosp 6, Beijing 100191, Peoples R China
3.Natl Clin Res Ctr Mental Disorders, Key Lab Mental Hlth, Bethesda, MD USA
4.Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
5.Guiyang Med Univ, Affiliated Hosp, Guiyang 550004, Peoples R China
6.Hebei Med Univ, Basic Med Coll, Dept Biochem & Mol Biol, Shijiazhuang 050017, Peoples R China
7.Hebei Med Univ, Inst Mental Hlth, Shijiazhuang 050031, Peoples R China
8.Hebei Med Univ, Hebei Brain Ageing & Cognit Neurosci Lab, Shijiazhuang 050031, Peoples R China
9.Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
10.Peking Univ, McGovern Inst Brain Res, PKU IDG, Beijing 100871, Peoples R China
Recommended Citation
GB/T 7714
Liu, Jian-Feng,Yang, Chang,Deng, Jia-Hui,et al. Role of Hippocampal beta-Adrenergic and Glucocorticoid Receptors in the Novelty-Induced Enhancement of Fear Extinction[J]. JOURNAL OF NEUROSCIENCE,2015,35(21):8308-8321.
APA Liu, Jian-Feng.,Yang, Chang.,Deng, Jia-Hui.,Yan, Wei.,Wang, Hui-Min.,...&Lu, Lin.(2015).Role of Hippocampal beta-Adrenergic and Glucocorticoid Receptors in the Novelty-Induced Enhancement of Fear Extinction.JOURNAL OF NEUROSCIENCE,35(21),8308-8321.
MLA Liu, Jian-Feng,et al."Role of Hippocampal beta-Adrenergic and Glucocorticoid Receptors in the Novelty-Induced Enhancement of Fear Extinction".JOURNAL OF NEUROSCIENCE 35.21(2015):8308-8321.
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