Augmented Reticular Thalamic Bursting and Seizures in Scn1a-Dravet Syndrome.
Augmented Reticular Thalamic Bursting and Seizures in Scn1a-Dravet Syndrome.
复制标题
Scn1a-Dravet 综合征中增强的网状丘脑破裂和癫痫发作。
DOI：
10.1016/j.celrep.2019.01.037
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发表时间：
2019
期刊：
影响因子：
8.8
通讯作者：
Delo
中科院分区：
文献类型：
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作者：
Ritter-Makinson,Stefanie;Clemente-Perez,Alexandra;Higashikubo,Bryan;Cho,FrancesS;Holden,StephanieS;Bennett,Eric;Chkhaidze,Ana;EelkmanRooda,OscarHJ;Cornet,Marie-Coralie;Hoebeek,FreekE;Yamakawa,Kazuhiro;Cilio,MariaRoberta;Delo
Scn1基因功能丧失会导致严重的癫痫性脑病，称为 Dravet 综合征 (DS)。皮质抑制神经元兴奋性降低被认为是 DS 癫痫发作的主要原因。相比之下，我们在这里发现丘脑抑制性神经元的兴奋性增强，从而促进非惊厥性癫痫发作，这是 DS 的一个突出但人们知之甚少的特征。在Scn1a功能丧失的DS小鼠模型中，网状丘脑细胞表现出异常长时间的放电，这是由钙激活钾SK通道的下调引起的。我们的研究支持一种机制，即 SK 活性丧失导致网状丘脑神经元变得过度兴奋并促进 DS 中的非惊厥性癫痫发作。我们认为，抑制性神经元的兴奋性降低在 DS 中并不是全局性的，并且 SK 通道等非 GABA 能机制可能是治疗的重要目标。
Loss of function in theScn1agene leads to a severe epileptic encephalopathy called Dravet syndrome (DS). Reduced excitability in cortical inhibitory neurons is thought to be the major cause of DS seizures. Here, in contrast, we show enhanced excitability in thalamic inhibitory neurons that promotes the non-convulsive seizures that are a prominent yet poorly understood feature of DS. In a mouse model of DS with a loss of function inScn1a, reticular thalamic cells exhibited abnormally long bursts of firing caused by the downregulation of calcium-activated potassium SK channels. Our study supports a mechanism in which loss of SK activity causes the reticular thalamic neurons to become hyperexcitable and promote non-convulsive seizures in DS. We propose that reduced excitability of inhibitory neurons is not global in DS and that non-GABAergic mechanisms such as SK channels may be important targets for treatment.