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Uncoupling nNOS-PSD-95 in the ACC can inhibit contextual fear generalization

Qin, Cheng, Bian, Xin-Lan, Cai, Cheng-Yun, Chen, Chen, Zhou, Ying, Lin, Yu-Hui, Tao, Yan, Wu, Hai-Yin, Chang, Lei, Luo, Chun-Xia, Zhu, Dong-Ya
Biochemical and biophysical research communications 2019 v.513 no.1 pp. 248-254
cortex, fearfulness, histone deacetylase, memory, neuronal nitric oxide synthase
A typical feature of the contextual fear memory is increased fear generalization with time. Though much attention has been given to the neural structures that underlie the long-term consolidation of a contextual fear memory, the molecular mechanisms regulating fear generalization remain unclear. We observed that retrieval of contextual fear in a novel context at a remote time point increased coupling of neuronal nitric oxide synthase (nNOS) with postsynaptic density-95 (PSD-95) and c-Fos expression in the anterior cingulate cortex (ACC). Disrupting nNOS-PSD-95 coupling in the ACC decreased the expression of Histone deacetylase 2 (HDAC2), and inhibited contextual fear generalization at a remote time point. Together, our findings reveal nNOS-PSD-95 interaction in the ACC could be a promising target to prevent or reverse contextual fear generalization.