Advanced wireless optogenetics and photometry system for neuroscience research

项目摘要/摘要 在过去的十年里，神经科学研究因许多技术进步而发生了革命性的变化。 光遗传学和荧光成像是两种截然不同、有时相辅相成的工具 神经科学研究在大脑主动性的背景下研究中枢和外周神经系统的科学。 然而，对潜在神经回路和生物学的高级审讯经常受到技术的阻碍 限制使用这些方法来研究不受束缚的、自由移动的自然行为 动物。用于光遗传学的传统光缆和与外部连接的笨重的金属套管 用于药理的机械泵对脆弱的神经组织造成重大损害，限制自然行为 在复杂、自然的3D环境中，影响社会互动和运动，以及 由于机械失配和微运动，导致生物/非生物界面的持续刺激。这些 缺点，再加上当前技术的昂贵设置，推动了创新技术的发展 工程设计，以提高保真度、易操作性、多功能性和高级大脑研究的范围 用活体动物模型进行研究。 我们在第二阶段的工作开发了构建现有系统级硬件和软件的能力，如 以及可扩展的制造方案，以制造我们的无线、无电池的光遗传学设备。穿过 通过这些努力，Neurolux在传播神经科学工具方面已经取得了实质性的成功 研究，在过去三年中，将用户基础增加到11个国家的80个实验室。拟开展的工作 阶段IIB专注于通过完善硬件的关键方面以及 扩展我们的功能，包括完全可植入、无线、无电池的荧光成像以进行监控 实时的神经活动，以一种利用我们现有硬件和软件的方式。具体地说， 拟议的工作将(1)开发具有先进功能的多机柜操作硬件，(2)推进长箱作业 具有主动、可编程控制光照强度的射程光遗传刺激器，以及(3)开发 具有集成光遗传刺激功能的选项的光电测光仪。

Project Summary/Abstract Neuroscience research over the last decade has been revolutionized by many technological advancements. Optogenetics and fluorescence imaging represent two distinct, and sometimes complementary tools used in neuroscience research to study the central and peripheral nervous systems in the context of the BRAIN initiative. Advanced interrogations of underlying neural circuits and biology are often frustrated, however, by technological limitations that prevent the use of these approaches to study natural behaviors of untethered, freely moving animals. Traditional fiber-optic cable for optogenetics and bulky metal cannulas connected with external mechanical pumps for pharmacology impart significant damage to fragile neural tissue, limit the natural behavior of freely moving animals, affect social interactions and movements in complex, naturalistic 3D environment, and lead to persistent irritation at the biotic/abiotic interface due to mechanical mismatch and micromotions. These drawbacks, together with the costly setup, of current technologies motivate the development of innovative engineering designs to improve fidelity, operational ease, versatility and range of advanced brain research studies with live animal models. Our work during Phase II developed capabilities to build our existing system-level hardware and software, as well as scalable manufacturing scheme to fabricate our wireless, battery-free optogenetics devices. Through these efforts, NeuroLux has already achieved substantial success in disseminating tools for neuroscience research, increasing user base to 80 laboratories in 11 countries in the last three years. The proposed work for Phase IIB focuses on further propelling our initial success by refining critical aspects of our hardware, as well as expanding our capabilities to include fully implantable, wireless, battery-free fluorescence imaging to monitor neural activity in real time, in a manner that leverages our current hardware and software. Specifically, the proposed work will (1) develop hardware for multi-enclosure operation with advanced features, (2) advance long- range optogenetic stimulators with active, programmable control over illumination intensity, and (3) develop optoelectronic photometers with options with integrated optogenetic stimulation capabilities.