title: Hippocampal Src kinase is required for novelty-induced enhancement of contextual fear extinction.
abstract: Exposure to a novel environment enhances the extinction of contextual fear through the "tagging-and-capture" process. However, the underlying molecular mechanisms of novelty-induced enhancement of fear extinction are still unclear. NMDA receptor activity was recently revealed to be required for the enhancement of fear extinction caused by exposure to novelty. Src family kinases (SFKs) act as a molecular hub for regulation of NMDA receptors. We hypothesized that SFKs might be involved in novelty-induced enhancement of fear extinction. We found that the enhancement of fear extinction induced by novelty exposure is accompanied by Src kinase phosphorylation and activation in a restricted time window. Furthermore, intrahippocampal infusion of SFKs inhibitor PP2 inhibits Src kinase phosphorylation and activation, attenuates the activation of NR2B-containing NMDA receptors, and thereby reverses the enhancement of fear extinction induced by novelty exposure. These results suggested that Src kinase may serve as a behavioral tag in the procedural enhancement of fear extinction by novelty exposure.
authors.affiliation: Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University; China; Department of Neurosurgery, The Second Affiliated Hospital, University of South China, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital, University of South China, China.
authors.forename: Ri-Chu
authors.initials: RC
authors.lastname: Liang
authors.affiliation: Department of Biology, University of Rochester, USA.
authors.forename: Zheng-Shan
authors.initials: ZS
authors.lastname: Liu
authors.affiliation: Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University; China.
authors.forename: Bing
authors.initials: B
authors.lastname: Luo
authors.affiliation: Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University; China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University; China.
authors.forename: Zi-Xiang
authors.initials: ZX
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital, University of South China, China. Electronic address: liaoys66@163.com.
authors.forename: Yong-Shi
authors.initials: YS
authors.lastname: Liao
authors.affiliation: Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University; China. Electronic address: wxguang@mail.sysu.edu.cn.
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Wang
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D005106:Exploratory Behavior; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D019061:src-Family Kinases
keywords: Fear extinction; Hippocampus; NMDA receptor; Novelty; Src kinase