title: Fear response failed to return in AAB extinction paradigm accompanied with increased NR2B and GluR1 per845 in hippocampal CA1.
abstract: Extinction is a well-known and important behavioral phenomenon that allows an organism to adapt its behavior to its environment. Previous studies have shown that the expression of extinction is highly context dependent, meanwhile, conditioning context, as part of fear memory, might have influence on extinction formation. To this end, we have conducted four different extinction paradigms in this study: extinction conducted in the conditioning context but tested in another, novel context (AAB); conditioning in one context and extinction and testing in the second (ABB); conditioning in context A, extinction training in context B, but test back to context A (ABA); and extinction training in a third context, context C (ACB). Additionally, a low dose of the GABAA agonist muscimol was used to temporarily inactivate CA1 to observe its effect in extinction. Our results showed that rats under the AAB, but not the ACB or ABA condition, showed a similar level of freezing compared with the typical ABB extinction paradigm. Moreover, muscimol infused into CA1 before extinction training resulted in impaired extinction and down-regulation of NR2B activity and phosphorylated GluR1 (at Ser845) in CA1, and the expression levels of NR2B and GluR1 were decreased significantly in the basolateral amygdala (BLA). Thus, CA1 may play an important role in the context-specific expression of fear extinction, and Ser845 may be a phosphorylation site in GluR1 in CA1, triggering the context-specific response of extinction memory.
authors.affiliation: Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: L
authors.initials: L
authors.lastname: Xue
authors.affiliation: Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Z D
authors.initials: ZD
authors.lastname: Li
authors.affiliation: Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Z X
authors.initials: ZX
authors.lastname: Chen
authors.affiliation: Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: X G
authors.initials: XG
authors.lastname: Wang
authors.affiliation: Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China. Electronic address: shiyanwei801102@hotmail.com.
authors.forename: Y W
authors.initials: YW
authors.lastname: Shi
authors.affiliation: Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China. Electronic address: hzhao@163.com.
authors.forename: H
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005108:Extinction, Psychological / Q000187:drug effects; D005239:Fear / Q000187:drug effects / Q000523:psychology*; D008297:Male; D009434:Neural Pathways; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor
keywords: ANOVA; BLA; CS; EXT; ITI; LTD; MAAB; MABA; MABB; MACB; MUS; Muscimol; N-methyl-D-aspartic acid; NMDA; PKA; PL; PTSD; SAAB; SABA; SABB; SACB; SD; US; analysis of variance; basolateral amygdala; conditional stimulus; extinction; fear memory; inter-trial interval; long term depression; muscimol; muscimol infusion in AAB version; muscimol infusion in ABA version; muscimol infusion in ABB version; muscimol infusion in ACB version; phosphorylation; post-traumatic stress disorder; prelimbic; protein kinase A; renewal; saline infusion in AAB version; saline infusion in ABA version; saline infusion in ABB version; saline infusion in ACB version; standard deviation; unconditional stimulus