Lee, Sukwon Song, Beomjong Kim, Jeongyeon Park, Kyungjoon Hong, Ingie An, Bobae Song, Sangho Lee, Jiwon Park, Sungmo Kim, Jihye Park, Dongeun Lee, C. Justin Kim, Kyungjin Shin, Ki Soon Tsien, Richard W. Choi, Sukwoo 2024-01-20T11:31:09Z 2024-01-20T11:31:09Z 2021-09-05 2013-10 1097-6256 https://pubs.kist.re.kr/handle/201004/127588 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. English NATURE PUBLISHING GROUP LONG-TERM POTENTIATION DEPENDENT NEURONAL-ACTIVITY AMPA RECEPTOR ENDOCYTOSIS SYNAPTIC PLASTICITY CONDITIONED FEAR GLUTAMATE RECEPTORS CHANNEL CONDUCTANCE KINASE-II EXTINCTION MEMORY GluA1 phosphorylation at serine 831 in the lateral amygdala is required for fear renewal Article 10.1038/nn.3491 1 NATURE NEUROSCIENCE, v.16, no.10, pp.1436 - + NATURE NEUROSCIENCE 16 10 1436 + scie scopus 000324795300016 2-s2.0-84884902554 Neurosciences Neurosciences & Neurology Article LONG-TERM POTENTIATION DEPENDENT NEURONAL-ACTIVITY AMPA RECEPTOR ENDOCYTOSIS SYNAPTIC PLASTICITY CONDITIONED FEAR GLUTAMATE RECEPTORS CHANNEL CONDUCTANCE KINASE-II EXTINCTION MEMORY