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.

journal_name

Nat Neurosci

journal_title

Nature neuroscience

authors

Lee S,Song B,Kim J,Park K,Hong I,An B,Song S,Lee J,Park S,Kim J,Park D,Lee CJ,Kim K,Shin KS,Tsien RW,Choi S

doi

10.1038/nn.3491

subject

Has Abstract

pub_date

2013-10-01 00:00:00

pages

1436-44

issue

10

eissn

1097-6256

issn

1546-1726

pii

nn.3491

journal_volume

16

pub_type

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