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- Title
HDAC1 Regulates Fear Extinction in Mice.
- Authors
Bahari-Javan, Sanaz; Maddalena, Andrea; Kerimoglu, Cemil; Wittnam, Jessica; Held, Torsten; Bähr, Mathias; Burkhardt, Susanne; Delalle, Ivanna; Kügler, Sebastian; Fischer, Andre; Sananbenesi, Farahnaz
- 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.
- Subjects
HISTONE deacetylase regulation; FEAR; EXTINCTION (Psychology); LABORATORY mice; NEUROBEHAVIORAL disorders; PATHOLOGICAL psychology; HISTONE deacetylase inhibitors; DEACETYLATION
- Publication
Journal of Neuroscience, 2012, Vol 32, Issue 15, p5062
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0079-12.2012