Hong SoonGweon, Lee Philip, Baraban Scott C, Lee Luke P
Department of Bioengineering Engineering, University of California, Berkeley, CA 94720, USA.
Berkeley Sensor and Actuator Center, University of California, Berkeley, CA 94720, USA.
Sci Rep. 2016 Jun 16;6:28248. doi: 10.1038/srep28248.
Zebrafish are a popular vertebrate model for human neurological disorders and drug discovery. Although fecundity, breeding convenience, genetic homology and optical transparency have been key advantages, laborious and invasive procedures are required for electrophysiological studies. Using an electrode-integrated microfluidic system, here we demonstrate a novel multichannel electrophysiology unit to record multiple zebrafish. This platform allows spontaneous alignment of zebrafish and maintains, over days, close contact between head and multiple surface electrodes, enabling non-invasive long-term electroencephalographic recording. First, we demonstrate that electrographic seizure events, induced by pentylenetetrazole, can be reliably distinguished from eye or tail movement artifacts, and quantifiably identified with our unique algorithm. Second, we show long-term monitoring during epileptogenic progression in a scn1lab mutant recapitulating human Dravet syndrome. Third, we provide an example of cross-over pharmacology antiepileptic drug testing. Such promising features of this integrated microfluidic platform will greatly facilitate high-throughput drug screening and electrophysiological characterization of epileptic zebrafish.
斑马鱼是用于人类神经疾病研究和药物发现的一种常用脊椎动物模型。尽管繁殖力、繁殖便利性、基因同源性和光学透明性是其关键优势,但电生理研究需要繁琐且具有侵入性的操作。在此,我们利用集成电极的微流控系统展示了一种新型多通道电生理装置,用于记录多条斑马鱼的电活动。该平台可使斑马鱼自发排列,并在数天内保持头部与多个表面电极的紧密接触,从而实现无创长期脑电图记录。首先,我们证明由戊四氮诱发的电图癫痫发作事件能够可靠地与眼睛或尾巴运动伪迹区分开来,并能用我们独特的算法进行定量识别。其次,我们展示了在模拟人类德雷维特综合征的scn1lab突变体癫痫发生进展过程中的长期监测。第三,我们提供了一个交叉药理学抗癫痫药物测试的例子。这种集成微流控平台的这些有前景的特性将极大地促进癫痫斑马鱼的高通量药物筛选和电生理特性分析。