KCC2 Overexpression Prevents the Paradoxical Seizure-Promoting Action of Somatic Inhibition Magloire, V., Cornford, J., Lieb, A., Kullmann, D. M., and Pavlov, I. Nat. Commun. 10, 1225. doi:10.1038/s41467-019-08933-4. Although cortical interneurons are apparently well-placed to suppress seizures, several recent reports have highlighted a paradoxical role of perisomatic-targeting parvalbumin-positive (PV+) interneurons in ictogenesis. Here, we use an acute in vivo model of focal cortical seizures in awake behaving mice, together with closed-loop optogenetic manipulation of PV+ interneurons, to investigate their function during seizures. We show that photo-depolarization of PV+ interneurons rapidly switches from an anti-ictal to a pro-ictal effect within a few seconds of seizure initiation. The pro-ictal effect of delayed photostimulation of PV+ interneurons was not shared with dendrite-targeting somatostatin-positive (SOM+) interneurons. We also show that this switch can be prevented by overexpression of the neuronal potassium-chloride co-transporter KCC2 in principal cortical neurons. These results suggest that strategies aimed at improving the ability of principal neurons to maintain a trans-membrane chloride gradient in the face of excessive network activity can prevent interneurons from contributing to seizure perpetuation.

中文翻译：

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当好警察变坏时：癫痫发作过程中表达中间神经元的小白蛋白的促分泌作用。

KCC2过度表达可预防体细胞抑制的反常促进癫痫发作的作用Magloire，V.，Cornford，J.，Lieb，A.，Kullmann，DM和Pavlov，I. Nat。社区 10，1225。doi：10.1038 / s41467-019-08933-4。尽管皮层中神经元显然可以很好地抑制癫痫发作，但最近的一些报道都强调了靶向靶向同位素的小白蛋白阳性（PV +）中神经元在信息生成中的反常作用。在这里，我们使用清醒行为小鼠局灶性皮质癫痫发作的急性体内模型，以及对PV + interneurons的闭环光遗传学操作，以研究其在癫痫发作期间的功能。我们显示，癫痫发作发作后的几秒钟内，PV +中间神经元的光去极化迅速从抗-抑制作用转变为保护作用。PV +中间神经元的延迟光刺激的促进作用与靶向树突的生长抑素阳性（SOM +）中间神经元没有共同作用。我们还表明，可以通过在主要皮层神经元中过表达神经元氯化钾共转运蛋白KCC2来防止此开关。这些结果表明，旨在提高主要神经元在网络活动过多的情况下维持跨膜氯化物梯度的能力的策略可以防止中间神经元导致癫痫发作持续。