The Rett syndrome protein MeCP2 regulates synaptic scaling.
The Rett syndrome protein MeCP2 regulates synaptic scaling.
复制标题
DOI：
10.1523/jneurosci.0175-11.2012
复制
发表时间：
2012-01-18
期刊：
影响因子：
--
通讯作者：
Ghosh A
中科院分区：
文献类型：
--
作者：
Qiu Z;Sylwestrak EL;Lieberman DN;Zhang Y;Liu XY;Ghosh A
突触伸缩是一种稳态突触可塑性的形式，其特征是整个细胞范围内突触强度的变化，以响应神经元总体活动水平的变化。在此，我们报道荷包牡丹碱诱导的神经元活动增加导致mEPSC幅度降低和AMPA受体亚单位GluR2表达减少。荷包牡丹碱处理还导致转录抑制因子MeCP2水平增加，该转录抑制因子与GluR2启动子以及辅助抑制因子HDAC1和mSin3A结合。通过shRNA表达或基因缺失下调MeCP2可阻断荷包牡丹碱诱导的GluR2表达和mEPSC幅度的降低。这些观察结果表明，MeCP2介导了活性依赖的突触伸缩，并提示由MeCP2突变引起的Rett综合征的病理生理学可能涉及突触电流活性依赖调节的缺陷。
Synaptic scaling is a form of homeostatic synaptic plasticity characterized by cell-wide changes in synaptic strength in response to changes in overall levels of neuronal activity. Here we report that bicuculline-induced increase in neuronal activity leads to a decrease in mEPSC amplitude and a decrease in expression of the AMPA receptor subunit GluR2 in rat hippocampal cultures. Bicuculline treatment also leads to an increase in the levels of the transcriptional repressor MeCP2, which binds to the GluR2 promoter along with the co-repressors HDAC1 and mSin3A. Down-regulation of MeCP2 by shRNA expression or genetic deletion blocks the bicuculline-induced decrease in GluR2 expression and mEPSC amplitude. These observations indicate that MeCP2 mediates activity-dependent synaptic scaling, and suggest that the pathophysiology of Rett syndrome, which is caused by mutations in MeCP2, may involve defects in activity-dependent regulation of synaptic currents.