title: Context and Auditory Fear are Differentially Regulated by HDAC3 Activity in the Lateral and Basal Subnuclei of the Amygdala.
abstract: Histone acetylation is a fundamental epigenetic mechanism that is dynamically regulated during memory formation. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) compete to modulate histone acetylation, allowing for rapid changes in acetylation in response to a learning event. HDACs are known to be powerful negative regulators of memory formation, but it is not clear whether this function depends on HDAC enzymatic activity per se. Here, we tested whether the enzymatic activity of an individual Class I HDAC, HDAC3, has a role in fear memory formation in subregions of the hippocampus and amygdala. We found that fear conditioning drove expression of the immediate early genes cFos and Nr4a2 in the hippocampus, which coincided with reduced HDAC3 occupancy at these promoters. Using a dominant-negative, deacetylase-dead point mutant virus (AAV-HDAC3(Y298H)-v5), we found that selectively blocking HDAC3 deacetylase activity in either the dorsal hippocampus or basal nucleus of the amygdala enhanced context fear without affecting tone fear. Blocking HDAC3 activity in the lateral nucleus of the amygdala, on the other hand, enhanced tone, but not context fear memory. These results show for the first time that the enzymatic activity of HDAC3 functions to negatively regulate fear memory formation. Further, HDAC3 activity regulates different aspects of fear memory in the basal and lateral subregions of the amygdala. Thus, the deacetylase activity of HDAC3 is a powerful negative regulator of fear memory formation in multiple subregions of the fear circuit.
authors.affiliation: Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, California, USA.|Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA.
authors.forename: Janine L
authors.initials: JL
authors.lastname: Kwapis
authors.affiliation: Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, California, USA.
authors.forename: Yasaman
authors.initials: Y
authors.lastname: Alaghband
authors.affiliation: Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, California, USA.
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: López
authors.affiliation: Department of Biological Sciences, Mount Holyoke College, South Hadley, Massachusetts, USA.
authors.forename: André O
authors.initials: AO
authors.lastname: White
authors.affiliation: Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, California, USA.
authors.forename: Rianne R
authors.initials: RR
authors.lastname: Campbell
authors.affiliation: Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, California, USA.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Dang
authors.affiliation: Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, California, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Rhee
authors.affiliation: Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, California, USA.
authors.forename: Ashley V
authors.initials: AV
authors.lastname: Tran
authors.affiliation: Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, California, USA.
authors.forename: Allison E
authors.initials: AE
authors.lastname: Carl
authors.affiliation: Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, California, USA.
authors.forename: Dina P
authors.initials: DP
authors.lastname: Matheos
authors.affiliation: Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, California, USA.|Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Wood
mesh_terms: D000818:Animals; D001307:Auditory Perception / Q000187:drug effects / Q000502:physiology; D066272:Basolateral Nuclear Complex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D000099186:Histone Deacetylase 3
chemical_list: D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D000099186:Histone Deacetylase 3