Microglia actively regulate the number of functional synapses.

Microglia actively regulate the number of functional synapses.
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小胶质细胞积极调节功能突触的数量。

DOI:
10.1371/journal.pone.0056293
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Tsirka SE
Tsirka SE
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ji K;Akgul G;Wollmuth LP;Tsirka SE

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小胶质细胞是中枢神经系统的免疫细胞。在生理环境中,它们高度运动的过程不断地观察局部脑实质,并短暂地接触突触元件。尽管最近的研究表明,小胶质细胞与突触的相互作用有助于突触在发育过程中的重塑,但小胶质细胞在突触生理学中的作用才刚刚开始被探索。为了评估这个问题,我们采用了电生理学方法,使用两种方法来处理培养中的小胶质细胞:用氯膦酸脂质体去除小胶质细胞的器官型海马脑切片,以及在培养的海马神经元中添加小胶质细胞。我们在这里表明,兴奋性突触后电流的频率在小胶质细胞枯竭的大脑切片中增加,与更高的突触密度一致,并且这种增强确保了小胶质细胞的损失,因为当小胶质细胞得到补充时,它是逆转的。相反,将小胶质细胞添加到神经元培养物中会降低突触活性,降低突触密度、脊柱数量、AMPA受体(GluA1)的表面表达和突触粘附分子的水平。综上所述,我们的研究结果表明,非激活的小胶质细胞通过调节中枢神经系统中功能性突触的数量来剧烈调节突触活动。
Microglia are the immunocompetent cells of the central nervous system. In the physiological setting, their highly motile processes continually survey the local brain parenchyma and transiently contact synaptic elements. Although recent work has shown that the interaction of microglia with synapses contributes to synaptic remodeling during development, the role of microglia in synaptic physiology is just starting to get explored. To assess this question, we employed an electrophysiological approach using two methods to manipulate microglia in culture: organotypic hippocampal brain slices in which microglia were depleted using clodronate liposomes, and cultured hippocampal neurons to which microglia were added. We show here that the frequency of excitatory postsynaptic current increases in microglia-depleted brain slices, consistent with a higher synaptic density, and that this enhancement ensures from the loss of microglia since it is reversed when the microglia are replenished. Conversely, the addition of microglia to neuronal cultures decreases synaptic activity and reduces the density of synapses, spine numbers, surface expression of AMPA receptor (GluA1), and levels of synaptic adhesion molecules. Taken together, our findings demonstrate that non-activated microglia acutely modulate synaptic activity by regulating the number of functional synapses in the central nervous system.
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