Designing low-cost, customizable high-density probes for acute and chronic neural recordings in rodents

总结 要了解大脑如何控制行为，需要研究大脑中不同神经元的动态活动。 在清醒行为动物的分布式神经回路中的神经元类型。目前，只有少数 然而，现有的技术允许研究人员记录数百人的活动， 在清醒的动物大脑中任意深度的数千个神经元。虽然 近年来，高密度微加工硅的发展取得了很大进展 探针，目前市售的探针提供很少或没有可定制的形态 不同的脑区和脑区内不同的细胞类型。更重要的是， 没有商业上可获得的具有集成刺激的高密度探针的解决方案 实现因果闭环实验的能力。在第一阶段，我们设计并制造了 可定制的高密度记录探头，用于急性头部固定记录， 制造策略。所得到的装置具有高的功能电极位点产率， 被beta-tester实验室成功用于生成具有良好信噪比的数据。我们 此外，还建立了一个在线图形界面，最终用户可以在其中设计他们的探头， 把他们的设计提交给制造商在第二阶段，神经动力学技术有限责任公司将开发 具有集成闭环功能的可定制高密度探头， 植入用于头部固定或能够自由移动的动物。第一个目标 我们的第二阶段建议是将光传输和电刺激功能集成到我们的 探针以实现闭环实验。光传输和电气的位置 刺激将是可定制的，以便客户可以指定他们想要的位置。第二 我们的目标是开发一种打包方法，包括构建一个特定于应用程序的 集成电路（ASIC）和一个可以控制所有集成功能的头级。的 组合包装设备将足够小，以使慢性实验中的任何头部- 固定或自由移动的动物。第三个目标是进行实验室测试和体内测试。 器械动物试验，以确定器械的基本功能和有效性。在 总之，无损检测将设计创新的闭环接口，使因果关系的研究 解决不同的大脑区域和神经元类型在大脑中的功能作用， 头部固定、活动自如的动物。这些类型的闭环设备可以进一步发展 用于神经植入物，以治疗神经系统疾病，如难治性癫痫，帕金森氏症， 其他震颤障碍。

SUMMARY Understanding how the brain controls behavior requires studying the dynamic activity of different types of neurons in distributed neural circuits in awake behaving animals. Currently, there are few technologies available however that allow researchers to record the activity of hundreds to thousands of neurons at arbitrary depth in the brains of awake, behaving animals. While there has been much recent progress in the development of high-density micro-fabricated silicon probes, current commercially available probes offer little to no customizability to the morphology of different brain regions and different cell types within brain regions. Even more importantly, there are no commercially available solutions of high-density probes with integrated stimulation capabilities enabling causal, closed-loop experimentation. In Phase I, we designed and fabricated customizable high-density recording probes for acute head-fixed recordings and streamlined our fabrication strategies. The resulting devices had high yields of functional electrode sites and were successfully used by beta-tester labs to generate data with good signal-to-noise ratios. We furthermore built an online graphical interface where end-users can design their probes and submit their designs for fabrication. In Phase II, Neural Dynamics Technologies LLC will develop customizable, high-density probes with integrated closed-loop capabilities that can be chronically implanted for use in animals that are either head-fixed or able to move around freely. The first aim of our Phase II proposal is to integrate light delivery and electrical stimulation capabilities onto our probes to enable closed-loop experimentation. The locations for light delivery and electrical stimulation will be customizable so that customers can specify their desired location. The second aim will be to develop a packaging approach that involves building an application specific integrated circuit (ASIC) and a head-stage that can control all integrated functionalities. The combined packaged device will be small enough to enable chronic experiments in either head- fixed or freely moving animals. The third aim will be to perform both bench-top testing and in vivo animal testing of devices to establish basic functionality and effectiveness of the devices. In summary, NDT will design innovative closed-loop interfaces that will enable causal studies addressing the functional role of different brain regions and neuron types in the brains of both head-fixed and freely moving animals. These types of closed-loop devices may be further evolved into neural implants to treat neurological diseases such as refractory epilepsy, Parkinson’s and other tremor disorders.