The histone deacetylase HDAC4 regulates long-term memory in Drosophila.
The histone deacetylase HDAC4 regulates long-term memory in Drosophila.
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DOI：
10.1371/journal.pone.0083903
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Scott MJ
中科院分区：
文献类型：
--
作者：
Fitzsimons HL;Schwartz S;Given FM;Scott MJ
越来越多的研究表明，组蛋白去乙酰化酶（HDAC）的药理学抑制与长期记忆的增强相关，目前的研究集中在确定个体HDAC在认知功能中发挥的作用。在这里，我们研究HDAC4在果蝇长期记忆形成中的作用。我们发现，HDAC4在成年蘑菇体（记忆形成的重要结构）中的过表达导致了长期求爱记忆的特定损伤，但对短期记忆没有影响。HDAC4催化突变体的过表达也废除了LTM，这表明一种独立于催化活性的作用模式。我们发现HDAC4的过度表达导致转录因子MEF2从相对均匀的分布通过细胞核重新分布到点状核体中，在那里它与HDAC4共定位。由于MEF2也参与了长期记忆的调节，这些数据表明HDAC4对长期记忆的抑制作用可能是通过与MEF2的相互作用。在相同的遗传背景下，我们还发现RNAi介导的HDAC4基因敲低会损害长期记忆，因此我们证明HDAC4不仅是长期记忆的抑制因子，而且还调节正常的记忆形成。
A growing body of research indicates that pharmacological inhibition of histone deacetylases (HDACs) correlates with enhancement of long-term memory and current research is concentrated on determining the roles that individual HDACs play in cognitive function. Here, we investigate the role of HDAC4 in long-term memory formation in Drosophila. We show that overexpression of HDAC4 in the adult mushroom body, an important structure for memory formation, resulted in a specific impairment in long-term courtship memory, but had no affect on short-term memory. Overexpression of an HDAC4 catalytic mutant also abolished LTM, suggesting a mode of action independent of catalytic activity. We found that overexpression of HDAC4 resulted in a redistribution of the transcription factor MEF2 from a relatively uniform distribution through the nucleus into punctate nuclear bodies, where it colocalized with HDAC4. As MEF2 has also been implicated in regulation of long-term memory, these data suggest that the repressive effects of HDAC4 on long-term memory may be through interaction with MEF2. In the same genetic background, we also found that RNAi-mediated knockdown of HDAC4 impairs long-term memory, therefore we demonstrate that HDAC4 is not only a repressor of long-term memory, but also modulates normal memory formation.
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影响因子：
16.2
作者：
Flavell, Steven W.;Kim, Tae-Kyung;Gray, Jesse M.;Harmin, David A.;Hemberg, Martin;Hong, Elizabeth J.;Markenscoff-Papadimitriou, Eirene;Bear, Daniel M.;Greenberg, Michael E.
通讯作者：
Greenberg, Michael E.
DOI：
10.1523/jneurosci.1882-10.2010
发表时间：
2010-12-08
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Akalal DB;Yu D;Davis RL
通讯作者：
Davis RL
影响因子：
4.8
作者：
Chan, JKL;Sun, LG;Wu, ZG
通讯作者：
Wu, ZG
影响因子：
4.7
作者：
Chawla, S;Vanhoutte, P;Bading, H
通讯作者：
Bading, H
影响因子：
2.5
作者：
Darcy, Michael J.;Calvin, Kate;Ouimet, Charles C.
通讯作者：
Ouimet, Charles C.