Genes and pathways associated with fear discrimination identified by genome-wide DNA methylation and RNA-seq analyses in nucleus accumbens in mice

Hao, Bo; Fan, Bu-Fang; Cao, Can-Can; Liu, Lu; Xuan, Shou-Min; Wang, Li; Gao, Zhen-Jie; Shi, Yan‐Wei; Wang, Xiaoguang; Zhao, Hu

doi:10.1016/j.pnpbp.2022.110643

Cited by 2 publications

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“…The discrimination index (DI) was calculated for evaluating the level of fear generalization ( Xu and Südhof, 2013 ; Hao et al, 2023 ). For individual animal, it was defined as:…”

Section: Methodsmentioning

confidence: 99%

mGluR5 in amygdala modulates fear memory generalization

Xuan

Su²,

Liang³

et al. 2023

Front. Behav. Neurosci.

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IntroductionFear memory generalization is regarded as the core characteristic of posttraumatic stress disorder (PTSD) development. However, the mechanism that contributes to the generalization of conditioned fear memory is still unclear. The generalization is generally considered to be a mismatch that occurs during memory consolidation.MethodsFoot shocks and tones were given as unconditioned stress and conditioned stress, respectively for fear conditioning training. Immunofluorescence staining, western blotting and qPCR were performed to determine the expression of different genes in amygdala of mice after fear conditioning training. Cycloheximide was used as a protein synthesis inhibitor and 2-methyl-6-phenylethynyl-pyridine was injected for mGluR5 inhibition.ResultsFear conditioning using caused incremental generalization, which was clearly observed during training. The density of c-Fos+ cells or the synaptic p-NMDAR expression did not differ with stress intensities. Strong-shock fear conditioning could induce significant mGluR5 de novo synthesis in the amygdala, which was not observed in the weak-shock group. Inhibition of mGluR5 impaired fear memory generalization induced by strong-shock fear conditioning, but the generalization level induced by weak-shock training was enhanced.DiscussionThese results indicated that mGluR5 in the amygdala is critical to the function of inappropriate fear memory generalization and suggested that this may be a potential target for the treatment of PTSD.

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“…The discrimination index (DI) was calculated for evaluating the level of fear generalization ( Xu and Südhof, 2013 ; Hao et al, 2023 ). For individual animal, it was defined as:…”

Section: Methodsmentioning

confidence: 99%