A novel carbon tipped single micro-optrode for combined optogenetics and electrophysiology

Optical microelectrodes (optrodes) are used in neuroscience to transmit light into the brain of a genetically modified animal to evoke and record electrical activity from light-sensitive neurons. Our novel micro-optrode solution integrates a light-transmitting 125 micrometer optical fiber and a 9 micrometer carbon monofilament to form an electrical lead element, which is contained in a borosilicate glass sheathing coaxial arrangement ending with a micrometer-sized carbon tip. This novel unit design is stiff and slender enough to be used for targeting deep brain areas, and may cause less tissue damage compared with previous models. The center-positioned carbon fiber is less prone to light-induced artifacts than side-lit metal microelectrodes previously presented. The carbon tip is capable of not only recording electrical signals of neuronal origin but can also provide valuable surface area for electron transfer, which is essential in electrochemical (voltammetry, amperometry) or microbiosensor applications. We present details of design and manufacture as well as operational examples of the newly developed single micro-optrode, which includes assessments of 1) carbon tip length–impedance relationship, 2) light transmission capabilities, 3) photoelectric artifacts in carbon fibers, 4) responses to dopamine using fast-scan cyclic voltammetry in vivo, and 5) optogenetic stimulation and spike or local field potential recording from the rat brain transfected with channelrhodopsin-2. With this work, we demonstrate that our novel carbon tipped single micro-optrode may open up new avenues for use in optogenetic stimulation when needing to be combined with extracellular recording, electrochemical, or microbiosensor measurements performed on a millisecond basis.

光学微电极（Optical microelectrodes，简称optrodes）被应用于神经科学领域，用于向基因修饰动物的脑内传输光线，以诱发并记录光敏神经元的电活动。本研究开发的新型微光电极方案集成了一根直径125微米的透光光纤与一根直径9微米的碳单丝，构成导电引线元件；该元件被封装于同轴排列的硼硅酸盐玻璃护套中，末端带有微米级碳纤维尖端。该新型器件设计兼具刚性与纤细度，可用于靶向深部脑区，且相较于前代模型，对脑组织的损伤更小。居中布置的碳纤维相较于此前报道的侧照式金属微电极，更不易产生光诱导伪影。该碳纤维尖端不仅能够记录神经元源性电信号，还可提供充足的电子转移表面积，这在电化学（伏安法、安培法）或微生物传感器应用中至关重要。本研究详述了新型单根微光电极的设计、制备方法与操作实例，评估内容包括：1）碳纤维尖端长度-阻抗关系；2）透光性能；3）碳纤维中的光电伪影；4）采用体内快速扫描循环伏安法检测多巴胺的响应；5）转染了通道视紫红质-2的大鼠脑内的光遗传刺激与锋电位或局部场电位记录。通过本研究，我们证实这款新型碳纤维尖端单根微光电极，可在需要结合毫秒级时序的胞外记录、电化学检测或微生物传感器测量时，为光遗传刺激应用开辟全新路径。