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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arabidopsis Proteins / metabolism
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CA1 Region, Hippocampal / cytology
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CA1 Region, Hippocampal / physiology
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
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Cells, Cultured
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Conditioning, Psychological / physiology
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Electric Stimulation
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Excitatory Postsynaptic Potentials / genetics
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Fear / physiology
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GABA Antagonists / pharmacology
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Histone Deacetylases / deficiency
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Histone Deacetylases / genetics
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Histone Deacetylases / metabolism*
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Humans
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In Vitro Techniques
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Intramolecular Transferases / metabolism
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Learning Disabilities / genetics
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / genetics
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Long-Term Potentiation / physiology*
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Maze Learning / physiology
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Memory / drug effects
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Memory / physiology*
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Memory Disorders / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Motor Activity / genetics
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Neurons / physiology*
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Patch-Clamp Techniques
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Picrotoxin / pharmacology
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Rotarod Performance Test
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Sodium Channel Blockers / pharmacology
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Synapses / genetics
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Synapses / physiology*
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Tetrodotoxin / pharmacology
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Transfection
Substances
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Arabidopsis Proteins
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GABA Antagonists
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Sodium Channel Blockers
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Picrotoxin
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Green Fluorescent Proteins
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Tetrodotoxin
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Hdac5 protein, mouse
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Histone Deacetylases
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Intramolecular Transferases
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marneral synthase, Arabidopsis