title: An essential role for histone deacetylase 4 in synaptic plasticity and memory formation.
abstract: Histone deacetylases (HDACs), a family of enzymes involved in epigenetic regulation, have been implicated in the control of synaptic plasticity, as well as learning and memory. Previous work has demonstrated administration of pharmacological HDAC inhibitors, primarily those targeted to class I HDACs, enhance learning and memory as well as long-term potentiation. However, a detailed understanding of the role of class II HDACs in these processes remains elusive. Here, we show that selective loss of Hdac4 in brain results in impairments in hippocampal-dependent learning and memory and long-term synaptic plasticity. In contrast, loss of Hdac5 does not impact learning and memory demonstrating unique roles in brain for individual class II HDACs. These findings suggest that HDAC4 is a crucial positive regulator of learning and memory, both behaviorally and at the cellular level, and that inhibition of Hdac4 activity may have unexpected detrimental effects to these processes.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Mi-Sung
authors.initials: MS
authors.lastname: Kim
authors.forename: M Waseem
authors.initials: MW
authors.lastname: Akhtar
authors.forename: Megumi
authors.initials: M
authors.lastname: Adachi
authors.forename: Melissa
authors.initials: M
authors.lastname: Mahgoub
authors.forename: Rhonda
authors.initials: R
authors.lastname: Bassel-Duby
authors.forename: Ege T
authors.initials: ET
authors.lastname: Kavalali
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Monteggia
mesh_terms: D000818:Animals; D029681:Arabidopsis Proteins / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics; D002478:Cells, Cultured; D003213:Conditioning, Psychological / Q000502:physiology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D005239:Fear / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006655:Histone Deacetylases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D019751:Intramolecular Transferases / Q000378:metabolism; D007859:Learning Disabilities / Q000235:genetics; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D045442:Rotarod Performance Test; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014162:Transfection
chemical_list: D029681:Arabidopsis Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D018756:GABA Antagonists; D049452:Green Fluorescent Proteins; D006655:Histone Deacetylases; D019751:Intramolecular Transferases; D010852:Picrotoxin; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; C498618:Hdac5 protein, mouse; C568454:marneral synthase, Arabidopsis