title: GluA1 phosphorylation at serine 831 in the lateral amygdala is required for fear renewal.
abstract: 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.
authors: 1] School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea. [2].
authors: Sukwon
authors: S
authors: Lee
authors: Beomjong
authors: B
authors: Song
authors: Jeongyeon
authors: J
authors: Kim
authors: Kyungjoon
authors: K
authors: Park
authors: Ingie
authors: I
authors: Hong
authors: Bobae
authors: B
authors: An
authors: Sangho
authors: S
authors: Song
authors: Jiwon
authors: J
authors: Lee
authors: Sungmo
authors: S
authors: Park
authors: Jihye
authors: J
authors: Kim
authors: Dongeun
authors: D
authors: Park
authors: C Justin
authors: CJ
authors: Lee
authors: Kyungjin
authors: K
authors: Kim
authors: Ki Soon
authors: KS
authors: Shin
authors: Richard W
authors: RW
authors: Tsien
authors: Sukwoo
authors: S
authors: Choi
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology* / Q000523:psychology; D008297:Male; D009924:Organ Culture Techniques; D010766:Phosphorylation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000235:genetics / Q000378:metabolism*
chemical_list: D018091:Receptors, AMPA; D012694:Serine
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