用于多脑区神经环路解析的新型光电极阵列

摘要

Optogenetics has been successfully applied to understand the mechanisms of neuropsychiatric diseases through the precise temporal control of specific neural circuitries. However, it remains a great challenge to integrate optogenetic modulation with electrophysiological recordings in multiple brain regions in vivo. In this study, a simpliifed method for the fabrication and electrochemical modiifcation of the multi-circuit optrode arrays was developed. The modiifed optrode arrays exhibited a signiifcantly higher capacitance and lower electrochemical impedance at 1 kHz as compared to unmodiifed optrodes. The optrode arrays were chronically implanted into the brain of VGAT-ChR2 transgenic mice. Spontaneous action potentials and local ifeld potentials as well as light-evoked responses were obtained in 4 different brain regions in vivo. The cross-area synchronizations were analyzed and the localizations of the implanted optrode arrays were conifrmed by 4', 6-diamidino-2-phenylindole immunolfuorescence staining. All these characteristics are greatly desired in optogenetic applications, and the fabrication method of the optrodes can be easily integrated with other in vivo techniques to build more advanced tools for the dissection of neural circuitry.%光遗传技术已被广泛用于神经环路的精确解析，帮助人们深入理解神经精神疾病的发病机制。然而在活体水平实现多脑区的光遗传调控和电生理记录仍然极具挑战。文章介绍了一种制备多脑区光电极阵列的方法。这种光电极阵列包含微电极支架和步进装置，可以同时对小鼠4个脑区的自发电生理信号(包括神经元放电和场电位)和光遗传调控后诱发的电生理变化进行记录。此外，还采用电化学修饰技术，显著降低了电极界面阻抗，提高了电生理记录信号的质量和稳定性。文章利用该光电极阵列对光遗传调控前后不同脑区之间神经元的同步化关系进行了分析，通过4',6-二脒基-2-苯基吲哚染色确定了光电极的植入位点。实验结果表明，这种多脑区光电极阵列适用于多脑区水平的研究，并且容易与其他在体研究方法结合，实现对特定神经环路的精确解析。