Experimental Epilepsy Group, Wallenberg Neuroscience Center, Lund University Hospital, Sölvegatan 17, BMC A11, 22184 Lund, Sweden.
Neuropharmacology. 2013 Jun;69:89-95. doi: 10.1016/j.neuropharm.2012.05.049. Epub 2012 Jun 12.
Optogenetic tools comprise a variety of different light-sensitive proteins from single-cell organisms that can be expressed in mammalian neurons and effectively control their excitability. Two main classes of optogenetic tools allow to either depolarize or hyperpolarize, and respectively generate or inhibit action potentials in selective populations of neurons. This opens unprecedented possibilities for delineating the role of certain neuronal populations in brain processing and diseases. Moreover, optogenetics may be considered for developing potential treatment strategies for brain diseases, particularly for excitability disorders such as epilepsy. Expression of the inhibitory halorhodopsin NpHR in hippocampal principal cells has been recently used as a tool to effectively control chemically and electrically induced epileptiform activity in slice preparations, and to reduce in vivo spiking induced by tetanus toxin injection in the motor cortex. In this review we give a comprehensive summary of what has been achieved so far in the field of epilepsy using optogenetics, and discuss some of the possible strategies that could be envisaged in the future. We also point out some of the challenges and pitfalls in relation to possible outcomes of using optogenetics for controlling network excitability, and associated brain diseases. This article is part of the Special Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'.
光遗传学工具包括来自单细胞生物的多种不同光敏感蛋白,这些蛋白可以在哺乳动物神经元中表达,并有效地控制其兴奋性。两种主要的光遗传学工具可以使神经元去极化或超极化,分别产生或抑制选择性神经元群体的动作电位。这为描绘特定神经元群体在大脑处理和疾病中的作用提供了前所未有的可能性。此外,光遗传学可能被认为是开发针对大脑疾病的潜在治疗策略的一种方法,特别是针对兴奋性障碍,如癫痫。最近,在海马主要神经元中表达抑制性盐敏视紫红质 NpHR 被用作一种工具,以有效地控制切片标本中化学和电诱导的癫痫样活动,并减少破伤风毒素注射引起的运动皮层中体内放电。在这篇综述中,我们全面总结了迄今为止在癫痫领域使用光遗传学所取得的成就,并讨论了未来可能设想的一些策略。我们还指出了与使用光遗传学控制网络兴奋性和相关大脑疾病的可能结果相关的一些挑战和陷阱。本文是题为“癫痫治疗的新靶点和新方法”的特刊的一部分。