光控ZIF驱动器:一种用于自由活动小鼠神经记录和光刺激的3D打印植入物及组装工具包。
OptoZIF Drive: a 3D printed implant and assembly tool package for neural recording and optical stimulation in freely moving mice.
作者信息
Freedman David S, Schroeder Joseph B, Telian Gregory I, Zhang Zhengyang, Sunil Smrithi, Ritt Jason T
机构信息
Boston University, Center for Neuroscience, USA.
出版信息
J Neural Eng. 2016 Dec;13(6):066013. doi: 10.1088/1741-2560/13/6/066013. Epub 2016 Oct 20.
OBJECTIVE
Behavioral neuroscience studies in freely moving rodents require small, light-weight implants to facilitate neural recording and stimulation. Our goal was to develop an integrated package of 3D printed parts and assembly aids for labs to rapidly fabricate, with minimal training, an implant that combines individually positionable microelectrodes, an optical fiber, zero insertion force (ZIF-clip) headstage connection, and secondary recording electrodes, e.g. for electromyography (EMG).
APPROACH
Starting from previous implant designs that position recording electrodes using a control screw, we developed an implant where the main drive body, protective shell, and non-metal components of the microdrives are 3D printed in parallel. We compared alternative shapes and orientations of circuit boards for electrode connection to the headstage, in terms of their size, weight, and ease of wire insertion. We iteratively refined assembly methods, and integrated additional assembly aids into the 3D printed casing.
MAIN RESULTS
We demonstrate the effectiveness of the OptoZIF Drive by performing real time optogenetic feedback in behaving mice. A novel feature of the OptoZIF Drive is its vertical circuit board, which facilities direct ZIF-clip connection. This feature requires angled insertion of an optical fiber that still can exit the drive from the center of a ring of recording electrodes. We designed an innovative 2-part protective shell that can be installed during the implant surgery to facilitate making additional connections to the circuit board. We use this feature to show that facial EMG in mice can be used as a control signal to lock stimulation to the animal's motion, with stable EMG signal over several months. To decrease assembly time, reduce assembly errors, and improve repeatability, we fabricate assembly aids including a drive holder, a drill guide, an implant fixture for microelectode 'pinning', and a gold plating fixture.
SIGNIFICANCE
The expanding capability of optogenetic tools motivates continuing development of small optoelectric devices for stimulation and recording in freely moving mice. The OptoZIF Drive is the first to natively support ZIF-clip connection to recording hardware, which further supports a decrease in implant cross-section. The integrated 3D printed package of drive components and assembly tools facilities implant construction. The easy interfacing and installation of auxiliary electrodes makes the OptoZIF Drive especially attractive for real time feedback stimulation experiments.
目的
在自由活动的啮齿动物身上进行行为神经科学研究需要小型、轻便的植入物,以方便神经记录和刺激。我们的目标是为实验室开发一套3D打印部件和组装辅助工具,以便在最少的培训下快速制造出一种植入物,该植入物结合了可单独定位的微电极、一根光纤、零插入力(ZIF夹)头端连接以及用于肌电图(EMG)等的辅助记录电极。
方法
从先前使用控制螺钉定位记录电极的植入物设计出发,我们开发了一种植入物,其微驱动器的主驱动体、保护壳和非金属部件通过3D并行打印。我们在电路板与头端连接的替代形状和方向方面,比较了它们的尺寸、重量和导线插入的难易程度。我们反复改进组装方法,并将额外的组装辅助工具集成到3D打印外壳中。
主要结果
我们通过在行为小鼠中进行实时光遗传学反馈,证明了OptoZIF驱动器的有效性。OptoZIF驱动器的一个新特点是其垂直电路板,它便于直接进行ZIF夹连接。这一特点要求以一定角度插入光纤,但光纤仍能从记录电极环的中心离开驱动器。我们设计了一种创新的两部分保护壳,可在植入手术期间安装,以方便与电路板进行额外连接。我们利用这一特点表明小鼠的面部EMG可作为控制信号,将刺激锁定到动物的运动上,且EMG信号在几个月内保持稳定。为了减少组装时间、减少组装错误并提高可重复性,我们制造了包括驱动器支架、钻孔导向器、用于微电极“固定”的植入固定装置以及镀金固定装置在内的组装辅助工具。
意义
光遗传学工具不断扩展的功能推动了用于自由活动小鼠刺激和记录的小型光电设备的持续发展。OptoZIF驱动器是首个原生支持与记录硬件进行ZIF夹连接的设备,这进一步支持减小植入物的横截面。驱动器组件和组装工具的集成3D打印包便于植入物的构建。辅助电极易于连接和安装,使得OptoZIF驱动器对实时反馈刺激实验特别有吸引力。