Optimization of Clear Optically Matched Panoramic Access Channel Technique (COMPACT) for large-scale deep-brain neurophotonic interface

透明光匹配全景接入信道技术(COMPACT)的优化 用于大规模脑深部神经光子接口 随着敏感分子指示剂和致动器的发展，神经光子学已经成为一种强大的 发现神经回路功能的基本原理的范例。然而，一个主要的障碍是 利用光来研究哺乳动物大脑深处的神经元是有限的访问深度。即使有了 多光子显微镜的进展，哺乳动物大脑成像的主要实现是 深度限制为~1毫米。小鼠大脑的大部分仍然无法获得细胞分辨率 测量，更不用说大型哺乳动物的大脑了。对脑深部区域进行成像，侵入性微缩 需要光学探头。这些光学探头的一个关键问题是微小的组织进入体积， 限制了要成像的神经元的数量，降低了实验的成功率。 对于大规模的脑深部神经光子接口，我们最近发展得很清楚 光匹配全景接入信道技术(COMPACT)，可以有效地提高系统的 组织进入量增加了~三个数量级。为了最大限度地发挥紧凑型平台的影响， 我们建议在三个主要领域对COMPACT进行优化。首先，我们将进一步小型化实施 紧凑型的。其次，我们将实现基于紧凑型光纤测光和光遗传学。这两个人 应用中，我们可以进一步将毛细血管直径缩小到160μm。可以插入多个毛细管 哺乳动物的大脑创造了神经光子接口的“高速公路”系统。这一发展将 用电极阵列探针补充现有的中尺度采样范例，通过提供 光学版全脑存取大容量记录和调制系统。三是大力发展 用于自由活动动物研究的头戴式双光子紧凑型系统。 为了对系统性能进行基准测试，我们将对神经元进行广泛的活体测量 活着的小鼠大脑中的结构和活动。具体地说，我们将量化和优化成像 分辨率、信噪比和毛细管外的最大成像深度。此外，我们还将简化 并使手术过程自动化，以便神经生物学家可以轻松采用。与 在技术进步发展的同时，我们还将致力于广泛传播以紧凑为主的 技术。除了科学出版物，我们还将开发一个类似于 Miniscope项目包括详细的机械和光学设计文件、系统校准和 校准程序、手术程序和定制的控制软件。最终的目标是使 紧凑，强大，交钥匙，并广泛可用来改变我们利用光来研究哺乳动物大脑的方式。

Optimization of Clear Optically Matched Panoramic Access Channel Technique (COMPACT) for large-scale deep-brain neurophotonic interface With the advance of sensitive molecular indicators and actuators, neurophotonics has become a powerful paradigm for discovering the principles underlying neural circuit functions. However, a major obstacle of using light to study neurons located deep in the mammalian brain is the limited access depth. Even with the advance of multiphoton microscopy, the majority of implementation for imaging the mammalian brain is limited to ~ 1 mm in depth. The majority of the mouse brain still remains inaccessible to cellular resolution measurement, not to mention the brain of larger mammals. To image deep brain regions, invasive miniature optical probes are required. One key issue with these optical probes is the tiny tissue access volume which limits the number of neurons to be imaged and reduces the success rate of experiments. Towards large-scale deep-brain neurophotonic interface, we have recently developed Clear Optically Matched Panoramic Access Channel Technique (COMPACT), which can effectively increase the tissue access volume by ~ three orders of magnitude. To maximize the impact of the COMPACT platform, we propose to optimize COMPACT in three major areas. First, we will further miniaturize the implementation of COMPACT. Second, we will enable COMPACT based fiber photometry and optogenetics. For these two applications, we can further reduce the capillary diameter to 160 μm. Multiple capillaries can be inserted in the mammalian brain to create the neurophotonic interface “highway” system. This development will complement the existing paradigm of mesoscale sampling with electrode array probes by providing an optical version of whole-brain-access high-capacity recording and modulation system. Third, we will develop head-mounted two-photon COMPACT system for freely moving animal studies. To benchmark the system performance, we will carry out extensive in vivo measurement of neuronal structure and activity in the living mouse brain. Specifically, we will quantify and optimize the imaging resolution, signal-to-noise ratio, and maximum imaging depth outside capillary. Moreover, we will simplify and automate the operation procedure so that it can be easily adopted by neurobiologists. With the progress of the technology development, we will also work to broadly disseminate the COMPACT based technologies. In addition to scientific publication, we will develop a comprehensive website similar to that of the Miniscope project to include the detailed mechanical and optical design files, system calibration and alignment routines, surgical procedures, and customized control software. The ultimate goal is to make COMPACT robust, turn-key, and broadly available to transform how we use light to study mammalian brains.