Fast spiking interneuron control of seizure propagation in a cortical slice model of focal epilepsy
Fast spiking interneuron control of seizure propagation in a cortical slice model of focal epilepsy
复制标题
DOI：
10.1113/jphysiol.2012.238154
复制
发表时间：
2013-02-01
影响因子：
5.5
通讯作者：
Carmignoto, Giorgio
中科院分区：
文献类型：
--
作者：
Cammarota, Mario;Losi, Gabriele;Carmignoto, Giorgio
在不同的局灶性癫痫动物模型中，前馈抑制会暂时阻止癫痫样发作性放电传播。然而，该信号的具体细胞来源以及抑制最终失效的机制尚不清楚。我们使用脑切片模型来研究从同一部位在精确时间重复诱发的局灶性发作放电如何在整个皮层传播。我们使用 Ca2+ 成像和同步单/双细胞记录来记录啮齿动物的锥体神经元 (PyNs) 和不同类别的中间神经元，包括分别在小白蛋白 (Pv)-快速尖峰 (FS) 和生长抑素 (Som) 中间神经元中表达绿色荧光蛋白的 G42 和 GIN 转基因小鼠。我们发现这两类中间神经元在病灶处产生发作性放电后不久就会密集放电。 PyN 中记录的抑制性弹幕与 Pv-FS 同时发生，但与 Som 中间神经元爆发放电不同。此外，抑制弹幕的强度随着 Pv-FS 中间神经元放电的增加或减少而增加或减少，但在 Som 中间神经元中则不然。发现由膜去极化引起的 Pv-FS 中间神经元放电损伤先于邻近锥体神经元的发作放电开始。这一事件可能是局部抑制崩溃的原因，局部抑制的崩溃使得空间上定义的 PyN 簇被招募到传播的发作放电中。我们的研究表明，Pv-FS 中间神经元是对抗发作性放电传播的抑制屏障的主要来源，并提出了靶向 Pv-FS 中间神经元代表一种新的治疗策略来预防人类局灶性癫痫发作的可能性。
In different animal models of focal epilepsy, seizure-like ictal discharge propagation is transiently opposed by feedforward inhibition. The specific cellular source of this signal and the mechanism by which inhibition ultimately becomes ineffective are, however, undefined. We used a brain slice model to study how focal ictal discharges that were repetitively evoked from the same site, and at precise times, propagate across the cortex. We used Ca2+ imaging and simultaneous single/dual cell recordings from pyramidal neurons (PyNs) and different classes of interneurons in rodents, including G42 and GIN transgenic mice expressing the green fluorescence protein in parvalbumin (Pv)-fast spiking (FS) and somatostatin (Som) interneurons, respectively. We found that these two classes of interneurons fired intensively shortly after ictal discharge generation at the focus. The inhibitory barrages that were recorded in PyNs occurred in coincidence with Pv-FS, but not with Som interneuron burst discharges. Furthermore, the strength of inhibitory barrages increased or decreased in parallel with increased or decreased firing in Pv-FS interneurons but not in Som interneurons. A firing impairment of Pv-FS interneurons caused by a membrane depolarization was found to precede ictal discharge onset in neighbouring pyramidal neurons. This event may account for the collapse of local inhibition that allows spatially defined clusters of PyNs to be recruited into propagating ictal discharges. Our study demonstrates that Pv-FS interneurons are a major source of the inhibitory barrages that oppose ictal discharge propagation and raises the possibility that targeting Pv-FS interneurons represents a new therapeutic strategy to prevent the generalization of human focal seizures.