Drebrin A Knockout Eliminates the Rapid Form of Homeostatic Synaptic Plasticity at Excitatory Synapses of Intact Adult Cerebral Cortex
Drebrin A Knockout Eliminates the Rapid Form of Homeostatic Synaptic Plasticity at Excitatory Synapses of Intact Adult Cerebral Cortex
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DOI：
10.1002/cne.22137
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发表时间：
2009-11-01
影响因子：
2.5
通讯作者：
Shirao, Tomoaki
中科院分区：
文献类型：
--
作者：
Aoki, Chiye;Kojima, Nobuhiko;Shirao, Tomoaki
稳态突触可塑性(HSP)对于维持神经元在动态范围内的兴奋性以及保护神经元免受可导致突触专一性破坏的无限制长时程增强(Turrigiano[2008]Cell 135：422-435)非常重要(Turrigiano[2008]Cell 135：422-435)。对这一现象背后的分子机制的了解仍然不完整，特别是对于快速形成的HSP。为了测试成年期的HSP是否依赖于一种F-肌动蛋白结合蛋白Drebrin A，研究人员培育了缺失了成体的Drebrin亚型(DAKO)但保留了胚胎亚型(Drebrin E)的小鼠。通过测定N-甲基-D-天冬氨酸受体(NMDAR)的NR2A亚单位在皮质表面应用NMDAR拮抗剂D-APV后是否能在脊髓内迅速上升来检测HSP。电子显微镜免疫细胞化学显示，正如预期的那样，D-APV处理野生型(WT)小鼠大脑皮质30分钟内，与非活性对映体L-APV处理的大脑半球基础水平相比，NR2-A免疫标记的棘细胞比例增加。这种差异在突触后膜和突触后密度(即突触连接)以及在脊柱内的非突触部位都是显著的，并且不伴随脊柱大小的变化。相比之下，D-APV治疗DAKO脑并没有增加NR2A在脊髓细胞质或突触连接处的标记，即使NR2A的基础水平与WT皮质没有显著差异。这些发现表明，快速(
Homeostatic synaptic plasticity (HSP) is important for maintaining neurons' excitability within the dynamic range and for protecting neurons from unconstrained long-term potentiation that can cause breakdown of synapse specificity (Turrigiano [2008] Cell 135:422-435). Knowledge of the molecular mechanism underlying this phenomenon remains incomplete, especially for the rapid form of HSP. To test whether HSP in adulthood depends on an F-actin binding protein, drebrin A, mice deleted of the adult isoform of drebrin (DAKO) but retaining the embryonic isoform (drebrin E) were generated. HSP was assayed by determining whether the NR2A subunit of N-methyl-D-aspartate receptors (NMDARs) can rise rapidly within spines following the application of an NMDAR antagonist, D-APV, onto the cortical surface. Electron microscopic immunocytochemistry revealed that, as expected, the D-APV treatment of wild-type (WT) mouse cortex increased the proportion of NR2A-immunolabeled spines within 30 minutes relative to basal levels in hemispheres treated with an inactive enantiomer, L-APV. This difference was significant at the postsynaptic membrane and postsynaptic density (i.e., synaptic junction) as well as at nonsynaptic sites within spines and was not accompanied by spine size changes. In contrast, the D-APV treatment of DAKO brains did not augment NR2A labeling within the spine cytoplasm or at the synaptic junction, even though basal levels of NR2A were not significantly different from those of WT cortices. These findings indicate that drebrin A is required for the rapid (