Experience Affects Critical Period Plasticity in the Visual Cortex through an Epigenetic Regulation of Histone Post-Translational Modifications
Experience Affects Critical Period Plasticity in the Visual Cortex through an Epigenetic Regulation of Histone Post-Translational Modifications
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DOI：
10.1523/jneurosci.1787-15.2016
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发表时间：
2016-03-23
影响因子：
5.3
通讯作者：
Sale, Alessandro
中科院分区：
文献类型：
--
作者：
Baroncelli, Laura;Scali, Manuela;Sale, Alessandro
在增强敏感性的早期阶段称为关键期（CP），单眼剥夺导致视觉皮层双眼神经元的反应发生变化，有利于非剥夺眼，这一过程称为眼优势（OD）可塑性。虽然OD可塑性的CP的时间过程可以通过针对GABA能抑制的遗传/药理学干预来调节，但增加的感觉-运动体验是否会影响这种主要的可塑性现象尚不清楚。暴露于丰富的环境（EE）加速了大鼠视皮层OD可塑性CP的关闭。组蛋白H3乙酰化在初级视觉皮层中受到发育调控，在富集的幼仔中早期可检测到增强的水平，染色质免疫沉淀显示BDNF P3启动子水平增加。组蛋白去乙酰化酶抑制剂SAHA（辛二酰苯胺异羟肟酸）在标准笼饲养的动物的管理模仿增加H3乙酰化观察到的视觉皮层，并导致OD可塑性的加速衰减。最后，暴露于EE在成年上调H3乙酰化，并通过重新开放的CP。这些研究结果表明，关键参与的表观遗传机制作为一个调解人的视觉皮层发育可塑性和影响EE OD可塑性。
During an early phase of enhanced sensitivity called the critical period (CP), monocular deprivation causes a shift in the response of visual cortex binocular neurons in favor of the nondeprived eye, a process named ocular dominance (OD) plasticity. While the time course of the CP for OD plasticity can be modulated by genetic/pharmacological interventions targeting GABAergic inhibition, whether an increased sensory-motor experience can affect this major plastic phenomenon is not known. Wereport that exposure to environmental enrichment (EE) accelerated the closure of the CP for OD plasticity in the rat visual cortex. Histone H3 acetylation was developmentally regulated in primary visual cortex, with enhanced levels being detectable early in enriched pups, and chromatin immunoprecipitation revealed an increase at the level of the BDNF P3 promoter. Administration of the histone deacetylase inhibitor SAHA (suberoylanilide hydroxamic acid) to animals reared in a standard cage mimicked the increase in H3 acetylation observed in the visual cortex and resulted in an accelerated decay of OD plasticity. Finally, exposure to EE in adulthood upregulated H3 acetylation and was paralleled by a reopening of the CP. These findings demonstrate a critical involvement of the epigenetic machinery as a mediator of visual cortex developmental plasticity and of the impact of EE on OD plasticity.