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WONOEP 评估:光遗传学工具抑制癫痫发作和探索癫痫发生的机制。

WONOEP appraisal: optogenetic tools to suppress seizures and explore the mechanisms of epileptogenesis.

机构信息

Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, United Kingdom.

出版信息

Epilepsia. 2014 Nov;55(11):1693-702. doi: 10.1111/epi.12804. Epub 2014 Oct 9.

DOI:10.1111/epi.12804
PMID:25303540
Abstract

Optogenetics is a novel technology that combines optics and genetics by optical control of microbial opsins, targeted to living cell membranes. The versatility and the electrophysiologic characteristics of the light-sensitive ion-channels channelrhodopsin-2 (ChR2), halorhodopsin (NpHR), and the light-sensitive proton pump archaerhodopsin-3 (Arch) make these optogenetic tools potent candidates in controlling neuronal firing in models of epilepsy and in providing insights into the physiology and pathology of neuronal network organization and synchronization. Opsins allow selective activation of excitatory neurons and inhibitory interneurons, or subclasses of interneurons, to study their activity patterns in distinct brain-states in vivo and to dissect their role in generation of synchrony and seizures. The influence of gliotransmission on epileptic network function is another topic of great interest that can be further explored by using light-activated Gq protein-coupled opsins for selective activation of astrocytes. The ever-growing optogenetic toolbox can also be combined with emerging techniques that have greatly expanded our ability to record specific subtypes of cortical and hippocampal neurons in awake behaving animals such as juxtacellular recording and two-photon guided whole-cell recording, to identify the specific subtypes of neurons that are altered in epileptic networks. Finally, optogenetic tools allow rapid and reversible suppression of epileptic electroencephalography (EEG) activity upon photoactivation. This review outlines the most recent advances achieved with optogenetic techniques in the field of epilepsy by summarizing the presentations contributed to the 13th ILAE WONOEP meeting held in the Laurentian Mountains, Quebec, in June 2013.

摘要

光遗传学是一种新颖的技术,通过光学控制微生物视蛋白,将光学与遗传学相结合,靶向活细胞膜。光敏感离子通道通道视紫红质-2(ChR2)、卤化视蛋白(NpHR)和光敏感质子泵archaerhodopsin-3(Arch)的多功能性和电生理特性,使这些光遗传学工具成为控制癫痫模型中神经元放电的有力候选工具,并深入了解神经元网络组织和同步的生理学和病理学。视蛋白允许选择性激活兴奋性神经元和抑制性中间神经元,或中间神经元的亚类,以研究它们在体内不同脑状态下的活动模式,并剖析它们在同步和癫痫发作中的作用。神经胶质传递对癫痫网络功能的影响是另一个非常感兴趣的话题,可以通过使用光激活的 Gq 蛋白偶联视蛋白来选择性激活星形胶质细胞来进一步研究。不断增长的光遗传学工具包还可以与新兴技术相结合,这些技术大大提高了我们在清醒活动动物中记录特定类型皮质和海马神经元的能力,例如共聚焦记录和双光子引导全细胞记录,以识别癫痫网络中改变的特定神经元类型。最后,光遗传学工具允许在光激活时快速可逆地抑制癫痫脑电图(EEG)活动。本综述通过总结 2013 年 6 月在魁北克 Laurentian Mountains 举行的第 13 届 ILAE WONOEP 会议上的演讲,概述了光遗传学技术在癫痫领域取得的最新进展。

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