On-demand optogenetic control of spontaneous seizures in temporal lobe epilepsy.

On-demand optogenetic control of spontaneous seizures in temporal lobe epilepsy.
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DOI:
10.1038/ncomms2376
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发表时间:
2013
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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颞叶癫痫是成人中最常见的癫痫类型,通常是医学难治性的,并且由于广泛的作用和长时间的尺度,目前的系统治疗具有主要的负面副作用。然而,颞叶癫痫发作往往出现在明显的临床行为之前的离散区域,使时间和空间特异性治疗在理论上成为可能。在这里,我们报告了自发性癫痫发作的逮捕使用实时,闭环,响应系统和体内光遗传学在颞叶癫痫小鼠模型。兴奋性主细胞的光遗传学抑制或代表<5%海马神经元的GABA能细胞亚群的激活在光应用时迅速停止癫痫发作。这些结果表明,自发性颞叶癫痫发作可以检测和终止调制特定的细胞群体在空间上受到限制的方式。建立在这些原则基础上的临床方法可以克服目前可用治疗方案的许多副作用。 成人颞叶癫痫并不总是对治疗有反应。Krook-Magnuson及其同事使用光遗传学分别在颞叶癫痫小鼠模型中抑制和激活兴奋性和抑制性神经元,并发现它们可以随时停止癫痫发作。
Temporal lobe epilepsy is the most common type of epilepsy in adults, is often medically refractory, and due to broad actions and long-time scales, current systemic treatments have major negative side-effects. However, temporal lobe seizures tend to arise from discrete regions before overt clinical behaviour, making temporally and spatially specific treatment theoretically possible. Here we report the arrest of spontaneous seizures using a real-time, closed-loop, response system and in vivo optogenetics in a mouse model of temporal lobe epilepsy. Either optogenetic inhibition of excitatory principal cells, or activation of a subpopulation of GABAergic cells representing <5% of hippocampal neurons, stops seizures rapidly upon light application. These results demonstrate that spontaneous temporal lobe seizures can be detected and terminated by modulating specific cell populations in a spatially restricted manner. A clinical approach built on these principles may overcome many of the side-effects of currently available treatment options. Temporal lobe epilepsy in adults does not always respond to treatment. Krook-Magnuson and colleagues use optogenetics to inhibit and activate excitatory and inhibitory neurons, respectively, in a mouse model of temporal lobe epilepsy, and find that they can stop seizures on a moment-to-moment basis.
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