LOW ACCUMULATION OF DREBRIN AT GLUTAMATERGIC POSTSYNAPTIC SITES ON GABAergic NEURONS
LOW ACCUMULATION OF DREBRIN AT GLUTAMATERGIC POSTSYNAPTIC SITES ON GABAergic NEURONS
复制标题
DOI：
10.1016/j.neuroscience.2010.06.043
复制
发表时间：
2010-09-15
期刊：
影响因子：
3.3
通讯作者：
Shirao, T.
中科院分区：
文献类型：
--
作者：
Hanamura, K.;Mizui, T.;Shirao, T.
谷氨酸能突触在谷氨酸能和 GABA 能神经元上形成。这两种类型的谷氨酸突触的电反应不同。高频刺激和突触后密度蛋白成分。然而，尚不清楚它们的肌动蛋白细胞骨架组成是否不同。在本研究中，我们使用谷氨酸脱羧酶 67 (GAD67)-GFP 敲入小鼠制备的海马神经元培养物，分析了接触 GABA 能和谷氨酸能神经元的谷氨酸突触肌动蛋白细胞骨架的差异。众所周知，树突棘中富含的结合树突蛋白的肌动蛋白丝在树突棘的形成中发挥着关键作用。免疫细胞化学分析表明，drebrin 在 GABA 能神经元以及谷氨酸能神经元的谷氨酸突触处积累。然而，GABA能神经元沿树突的drebrin簇密度明显低于谷氨酸能神经元。此外，GABA能神经元上谷氨酸能突触处积聚的drebrin水平低于谷氨酸能神经元。在过度表达drebrin的神经元中，GABA能神经元和谷氨酸能神经元中的drebrin簇密度和积累水平相似，表明GABA能神经元谷氨酸能突触后位点的低drebrin水平可能是因为GABA能神经元表达低水平的drebrin。另一方面，药理学分析表明，drebrin 的突触后定位取决于 GABA 能和谷氨酸能神经元中的肌动蛋白细胞骨架组织。这些结果共同表明，尽管 GABA 能神经元和谷氨酸能神经元共享影响 Drebrin 定位的共同调节系统，但 GABA 能神经元上形成的 Drebrin 阳性谷氨酸突触的密度低于谷氨酸能神经元上的密度。这可能是由于 GABA 能神经元中 Drebrin 的低表达所致。 (C) 2010 国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Glutamatergic synapses form onto both glutamatergic and GABAergic neurons. These two types of glutamatergic synapses differ in their electrical responses. to high-frequency stimulation and postsynaptic density protein composition. However, it is not known whether they differ in the actin cytoskeleton composition. In the present study, we used hippocampal neuronal cultures prepared from glutamate decarboxylase 67 (GAD67)-GFP knock-in mice and analyzed the differences in the actin cytoskeleton at glutamatergic synapses contacting GABAergic and glutamatergic neurons. Drebrin-binding actin filaments enriched in dendritic spines are known to play a pivotal role in spine formation. Immunocytochemical analyses demonstrated that drebrin accumulated at glutamatergic synapses on GABAergic neurons as well as at those on glutamatergic neurons. However, the density of drebrin clusters along dendrites in GABAergic neurons was significantly lower than those of glutamatergic neurons. Furthermore, the level of drebrin accumulating at glutamatergic synapses was lower on GABAergic neurons than on glutamatergic neurons. In neurons overexpressing drebrin, drebrin cluster density and accumulation levels in GABAergic and glutamatergic neurons were similar, suggesting that the low drebrin levels in the glutamatergic postsynaptic sites on GABAergic neurons may be because GABAergic neurons express low levels of drebrin. On the other hand, pharmacological analysis demonstrated that the postsynaptic localization of drebrin depended on actin cytoskeleton organization in both GABAergic and glutamatergic neurons. Together these results indicated that, although GABAergic and glutamatergic neurons share common regulatory systems affecting drebrin localization, the density of drebrin-positive glutamatergic synapses formed on GABAergic neurons is lower than those on glutamatergic neurons. This is probably due to the low expression of drebrin in GABAergic neurons. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.