Lillis Kyle P, Dulla Chris, Maheshwari Atul, Coulter Douglas, Mody Istvan, Heinemann Uwe, Armbruster Moritz, Žiburkus Jokūbas
Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, U.S.A; Harvard Medical School, Boston, Massachusetts, U.S.A.
Epilepsia. 2015 Apr;56(4):505-13. doi: 10.1111/epi.12939. Epub 2015 Feb 28.
Great advancements have been made in understanding the basic mechanisms of ictogenesis using single-cell electrophysiology (e.g., patch clamp, sharp electrode), large-scale electrophysiology (e.g., electroencephalography [EEG], field potential recording), and large-scale imaging (magnetic resonance imaging [MRI], positron emission tomography [PET], calcium imaging of acetoxymethyl ester [AM] dye-loaded tissue). Until recently, it has been challenging to study experimentally how population rhythms emerge from cellular activity. Newly developed optical imaging technologies hold promise for bridging this gap by making it possible to simultaneously record the many cellular elements that comprise a neural circuit. Furthermore, easily accessible genetic technologies for targeting expression of fluorescent protein-based indicators make it possible to study, in animal models of epilepsy, epileptogenic changes to neural circuits over long periods. In this review, we summarize some of the latest imaging tools (fluorescent probes, gene delivery methods, and microscopy techniques) that can lead to the advancement of cell- and circuit-level understanding of epilepsy, which in turn may inform and improve development of next generation antiepileptic and antiepileptogenic drugs.
在利用单细胞电生理学(如膜片钳、尖锐电极)、大规模电生理学(如脑电图[EEG]、场电位记录)以及大规模成像(磁共振成像[MRI]、正电子发射断层扫描[PET]、乙酰氧基甲基酯[AM]染料加载组织的钙成像)来理解癫痫发生的基本机制方面已经取得了巨大进展。直到最近,通过实验研究群体节律如何从细胞活动中产生一直具有挑战性。新开发的光学成像技术有望弥合这一差距,因为它能够同时记录构成神经回路的众多细胞成分。此外,用于靶向基于荧光蛋白的指示剂表达的易于获取的遗传技术,使得在癫痫动物模型中长时间研究神经回路的致痫性变化成为可能。在这篇综述中,我们总结了一些最新的成像工具(荧光探针、基因递送方法和显微镜技术),这些工具可以推动对癫痫在细胞和回路水平的理解,进而可能为下一代抗癫痫和抗癫痫药物的开发提供信息并加以改进。