Interneuron Desynchronization Precedes Seizures in a Mouse Model of Dravet Syndrome
Interneuron Desynchronization Precedes Seizures in a Mouse Model of Dravet Syndrome
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DOI：
10.1523/jneurosci.2370-19.2020
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发表时间：
2020-03-25
影响因子：
5.3
通讯作者：
Goldberg, Ethan M.
中科院分区：
文献类型：
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作者：
Tran, Conny H.;Vaiana, Michael;Goldberg, Ethan M.
反复发作定义为癫痫，是大脑电活动的一过性异常。癫痫发作的机制基础，以及明确的神经元亚型在癫痫病理生理学中的作用，目前仍知之甚少。我们对雄性和雌性Drave1a综合征(Scn1a(+/-))小鼠在温度诱导癫痫发作期间的新皮质进行了活体双光子钙成像，这是一种具有显著温度敏感型癫痫的神经发育障碍。在安静清醒、基线状态和核心体温升高时，Scn1a(+/-)组推测的主细胞和小白蛋白阳性中间神经元(PV-INS)的平均活性均高于野生型对照组。然而，野生型PV-INS表现出对温度升高的渐进同步反应，这是Scn1a(+/-)小鼠的PV-INS所不存在的。因此，在Scn1a(+/-)小鼠中，PV-IN活性在发作间歇期保持不变，但在癫痫发作前表现出同步性降低。我们推测，PV-IN同步性受损可能参与了DraveT综合征患者在体温诱发癫痫发作过程中向癫痫发作状态的转变。
Recurrent seizures, which define epilepsy, are transient abnormalities in the electrical activity of the brain. The mechanistic basis of seizure initiation, and the contribution of defined neuronal subtypes to seizure pathophysiology, remains poorly understood. We performed in vivo two-photon calcium imaging in neocortex during temperature-induced seizures in male and female Dravet syndrome (Scn1a(+/-)) mice, a neurodevelopmental disorder with prominent temperature-sensitive epilepsy. Mean activity of both putative principal cells and parvalbumin-positive interneurons (PV-INs) was higher in Scn1a(+/-) relative to wild-type controls during quiet wakefulness at baseline and at elevated core body temperature. However, wild-type PV-INs showed a progressive synchronization in response to temperature elevation that was absent in PV-INs from Scn1a(+/-) mice. Hence, PV-IN activity remains intact interictally in Scn1a(+/-) mice, yet exhibits decreased synchrony immediately before seizure onset. Wesuggest that impaired PV-IN synchronization may contribute to the transition to the ictal state during temperature-induced seizures in Dravet syndrome.