Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093-0366, USA.
J Neurosci. 2012 Jan 18;32(3):989-94. doi: 10.1523/JNEUROSCI.0175-11.2012.
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 corepressors HDAC1 and mSin3A. Downregulation 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.
突触可塑性是一种内稳态突触可塑性，其特征是在神经元活动的整体水平发生变化时，突触强度在细胞范围内发生变化。在这里，我们报告说，电刺激诱导的神经元活动增加会导致大鼠海马培养物中 mEPSC 幅度降低和 AMPA 受体亚基 GluR2 表达减少。电刺激处理还会导致转录抑制因子 MeCP2 的水平增加，MeCP2 与核心抑制因子 HDAC1 和 mSin3A 一起结合到 GluR2 启动子上。通过 shRNA 表达或基因缺失下调 MeCP2 会阻止电刺激诱导的 GluR2 表达和 mEPSC 幅度降低。这些观察结果表明，MeCP2 介导了活动依赖性突触可塑性，并且提示 Rett 综合征的病理生理学，其是由 MeCP2 突变引起的，可能涉及突触电流活动依赖性调节的缺陷。
