GluA1 phosphorylation at serine 831 in the lateral amygdala is required for fear renewal
- GluA1 phosphorylation at serine 831 in the lateral amygdala is required for fear renewal
- Sukwon Lee; Beomjong Song; 김정연; Kyungjoon Park; Ingie Hong; Bobae An; 송상호; Jiwon Lee; Sungmo Park; Jihye Kim; Dongeun Park; 이창준; Kyungjin Kim; Ki Soon Shin; Richard W Tsien; Sukwoo Choi
- Issue Date
- Nature neuroscience
- VOL 16, NO 10, 1436-1444
- Fear renewal, a widely pursued model of post-traumatic stress disorder and phobias, refers to the context-specific relapse of conditioned fear after extinction. However, its molecular mechanisms are largely unknown. We found that renewal-inducing stimuli, generally believed to be insufficient to induce synaptic plasticity, enhanced excitatory synaptic strength, activity of synaptic GluA2-lacking AMPA receptors and Ser831 phosphorylation of synaptic surface GluA1 in the lateral nucleus of the amygdala (LAn) of fear-extinguished rats. Consistently, the induction threshold for LAn synaptic potentiation was considerably lowered after extinction, and renewal occluded this low-threshold potentiation. The low-threshold potentiation (a potential cellular substrate for renewal), but not long-term potentiation, was attenuated by dialysis into LAn neurons of a GluA1-derived peptide that competes with Ser831-phosphorylated GluA1. Microinjections of the same peptide into the LAn attenuated fear renewal, but not fear learning. Our findings suggest that GluA1 phosphorylation constitutes a promising target for clinical treatment of aberrant fear-related disorders.
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