title: Consolidation of fear extinction requires protein synthesis in the medial prefrontal cortex.
abstract: Extinction of conditioned fear is thought to form a long-term memory of safety, but the neural mechanisms are poorly understood. Consolidation of extinction learning in other paradigms requires protein synthesis, but the involvement of protein synthesis in extinction of conditioned fear remains unclear. Here, we show that rats infused intraventricularly with the protein synthesis inhibitor anisomycin extinguished normally within a session but were unable to recall extinction the following day. Anisomycin-treated rats showed no savings in the rate of re-learning of extinction, consistent with amnesia for extinction training. The identical effect was observed when anisomycin was microinfused into the medial prefrontal cortex (mPFC) but not the insular cortex. Furthermore, we observed that extinction training increased c-Fos levels in the mPFC but not in the insular cortex, consistent with extinction-induced gene expression in the mPFC. These findings extend previous lesion and unit-recording data by demonstrating that the mPFC is a critical storage site for extinction memory, rather than simply a pathway for expression of extinction. Understanding consolidation of fear extinction could lead to new treatments for anxiety disorders in which fear extinction is thought to be compromised.
authors.affiliation: Department of Physiology, Ponce School of Medicine, Ponce, Puerto Rico 00732.
authors.forename: Edwin
authors.initials: E
authors.lastname: Santini
authors.forename: Hong
authors.initials: H
authors.lastname: Ge
authors.forename: Keqin
authors.initials: K
authors.lastname: Ren
authors.forename: Sandra
authors.initials: S
authors.lastname: Peña de Ortiz
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Quirk
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000008:administration & dosage / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D005239:Fear / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011500:Protein Synthesis Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D000841:Anisomycin