GluA1 phosphorylation at serine 831 in the lateral amygdala is required for fear renewal

Sukwon Lee; Beomjong Song; Jeongyeon Kim; Kyungjoon Park; Ingie Hong; Bobae An; Sangho Song; Jiwon Lee; Sungmo Park; Jihye Kim; Dongeun Park; C. Justin Lee; Kyungjin Kim; Ki Soon Shin; Richard W. Tsien; Sukwoo Choi

doi:10.1038/nn.3491

GluA1 phosphorylation at serine 831 in the lateral amygdala is required for fear renewal

Sukwon Lee, Beomjong Song, Jeongyeon Kim, Kyungjoon Park, Ingie Hong, Bobae An, Sangho Song, Jiwon Lee, Sungmo Park, Jihye Kim, Dongeun Park, C. Justin Lee, Kyungjin Kim, Ki Soon Shin, Richard W. Tsien, Sukwoo Choi

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40 Citations (Scopus)

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-relateddisorders.

Original language	English
Pages (from-to)	1436-1444
Number of pages	9
Journal	Nature Neuroscience
Volume	16
Issue number	10
DOIs	https://doi.org/10.1038/nn.3491
Publication status	Published - Oct 2013

Bibliographical note

Funding Information:
This paper is dedicated in loving memory to Sang-Soon Choi. We thank P. Sah for his valuable comments on our manuscript. This work was supported by a National Research Foundation of Korea grant funded by the Ministry of Education, Science and Technology (No. 2011-0018209, S.C.), by the Original Technology Research Program for Brain Science through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (No. 2011-0019226, S.C.) and by the Korean World Class Institute program (C.J.L.). B.S., Jeongyeon Kim, K.P., I.H., B.A., S.S., J.L., S.P. and Jihye Kim were supported by Brain Korea 21 Research Fellowships from the Korean Ministry of Education.

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@article{ccdc330b3252473897e22b731c4abd4d,

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-relateddisorders.",

author = "Sukwon Lee and Beomjong Song and Jeongyeon Kim and Kyungjoon Park and Ingie Hong and Bobae An and Sangho Song and Jiwon Lee and Sungmo Park and Jihye Kim and Dongeun Park and Lee, {C. Justin} and Kyungjin Kim and Shin, {Ki Soon} and Tsien, {Richard W.} and Sukwoo Choi",

note = "Funding Information: This paper is dedicated in loving memory to Sang-Soon Choi. We thank P. Sah for his valuable comments on our manuscript. This work was supported by a National Research Foundation of Korea grant funded by the Ministry of Education, Science and Technology (No. 2011-0018209, S.C.), by the Original Technology Research Program for Brain Science through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (No. 2011-0019226, S.C.) and by the Korean World Class Institute program (C.J.L.). B.S., Jeongyeon Kim, K.P., I.H., B.A., S.S., J.L., S.P. and Jihye Kim were supported by Brain Korea 21 Research Fellowships from the Korean Ministry of Education.",

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AU - Lee, Sukwon

AU - Song, Beomjong

AU - Kim, Jeongyeon

AU - Park, Kyungjoon

AU - Hong, Ingie

AU - An, Bobae

AU - Song, Sangho

AU - Lee, Jiwon

AU - Park, Sungmo

AU - Kim, Jihye

AU - Park, Dongeun

AU - Lee, C. Justin

AU - Kim, Kyungjin

AU - Shin, Ki Soon

AU - Tsien, Richard W.

AU - Choi, Sukwoo

N1 - Funding Information: This paper is dedicated in loving memory to Sang-Soon Choi. We thank P. Sah for his valuable comments on our manuscript. This work was supported by a National Research Foundation of Korea grant funded by the Ministry of Education, Science and Technology (No. 2011-0018209, S.C.), by the Original Technology Research Program for Brain Science through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (No. 2011-0019226, S.C.) and by the Korean World Class Institute program (C.J.L.). B.S., Jeongyeon Kim, K.P., I.H., B.A., S.S., J.L., S.P. and Jihye Kim were supported by Brain Korea 21 Research Fellowships from the Korean Ministry of Education.

PY - 2013/10

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AB - 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-relateddisorders.

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ER -

GluA1 phosphorylation at serine 831 in the lateral amygdala is required for fear renewal

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