TY - JOUR
T1 - An essential role for histone deacetylase 4 in synaptic plasticity and memory formation
AU - Kim, Mi Sung
AU - Akhtar, M. Waseem
AU - Adachi, Megumi
AU - Mahgoub, Melissa
AU - Bassel-Duby, Rhonda S
AU - Kavalali, Ege T
AU - Olson, Eric N
AU - Monteggia, Lisa M
PY - 2012/8/8
Y1 - 2012/8/8
N2 - 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.
AB - 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.
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U2 - 10.1523/JNEUROSCI.2089-12.2012
DO - 10.1523/JNEUROSCI.2089-12.2012
M3 - Article
C2 - 22875922
AN - SCOPUS:84864862726
SN - 0270-6474
VL - 32
SP - 10879
EP - 10886
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 32
ER -