title: HDAC1 regulates fear extinction in mice.
abstract: Histone acetylation has been implicated with the pathogenesis of neuropsychiatric disorders and targeting histone deacetylases (HDACs) using HDAC inhibitors was shown to be neuroprotective and to initiate neuroregenerative processes. However, little is known about the role of individual HDAC proteins during the pathogenesis of brain diseases. HDAC1 was found to be upregulated in patients suffering from neuropsychiatric diseases. Here, we show that virus-mediated overexpression of neuronal HDAC1 in the adult mouse hippocampus specifically affects the extinction of contextual fear memories, while other cognitive abilities were unaffected. In subsequent experiments we show that under physiological conditions, hippocampal HDAC1 is required for extinction learning via a mechanism that involves H3K9 deacetylation and subsequent trimethylation of target genes. In conclusion, our data show that hippocampal HDAC1 has a specific role in memory function.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, 37075 Göttingen, Germany.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Bahari-Javan
authors.forename: Andrea
authors.initials: A
authors.lastname: Maddalena
authors.forename: Cemil
authors.initials: C
authors.lastname: Kerimoglu
authors.forename: Jessica
authors.initials: J
authors.lastname: Wittnam
authors.forename: Torsten
authors.initials: T
authors.lastname: Held
authors.forename: Mathias
authors.initials: M
authors.lastname: Bähr
authors.forename: Susanne
authors.initials: S
authors.lastname: Burkhardt
authors.forename: Ivanna
authors.initials: I
authors.lastname: Delalle
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kügler
authors.forename: Andre
authors.initials: A
authors.lastname: Fischer
authors.forename: Farahnaz
authors.initials: F
authors.lastname: Sananbenesi
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D004597:Electroshock; D005106:Exploratory Behavior / Q000502:physiology; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology*; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D009474:Neurons / Q000378:metabolism; D004856:Postural Balance / Q000502:physiology; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D021641:Recognition, Psychology / Q000502:physiology; D013216:Reflex, Startle / Q000502:physiology; D013550:Swimming / Q000523:psychology
chemical_list: D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D011725:Pyridines; C118739:entinostat; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1