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 Neuroscijournal_title
Nature neuroscienceauthors
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 Sdoi
10.1038/nn.3491subject
Has Abstractpub_date
2013-10-01 00:00:00pages
1436-44issue
10eissn
1097-6256issn
1546-1726pii
nn.3491journal_volume
16pub_type
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