High Spatiotemporal Resolution Neural Recording System Using Active Sensing

项目摘要/摘要 研究复杂的神经动力学和大脑的认知功能需要非 具有高空间和时间分辨率的侵入式记录工具。荧光成像/显微技术就是其中之一 用于高空间分辨率记录神经元群体活动的最先进技术。 然而，现有的荧光神经成像技术通常速度有限，提供的 而不是几百帧每秒(或几毫秒的时间分辨率)。这不仅是有限的 受技术障碍(例如相机和/或光束扫描仪的低速)的限制，但也受到 微细的神经元结构发出的低信号水平。毫秒或更慢 时间分辨率基本上排除了对产生和传播的精确定时的测量 神经元棘波，这是神经信号的关键组成部分。在这个研发项目中，实物 科学公司(PSI)、达特茅斯学院以及麻省理工学院和哈佛大学的博德研究所提议 开发并演示一种新的荧光神经成像技术，使高速 记录多个神经元的膜电位。这项技术结合了两种互补的 实现亚微米空间和亚毫秒并行神经元记录的成像通道 时间分辨率。高速记录功能是使用基于 高灵敏度单点探测器和高速空间光调制器(SLM)。在第一阶段， 我们通过对钙标记的培养神经元进行成像，证明了该技术的可行性。 电压指示荧光传感器。在拟建的第二期工程中，我们会提升技术和 进一步证明了它在神经科学研究中的价值。第二阶段的原型将包括一款通用的 高时空分辨率传感器，兼容各种成像设置，包括头戴式 微型荧光显微镜。两个第二阶段的原型将交付给合作研究所 性能测试。测试实验将集中展示高时空分辨率 记录在体大脑神经元胞体和亚细胞结构的快动作电位 (例如，树突和突触)的神经元培养或脑片使用遗传编码的电压传感器。 这一研发项目将带来一种可靠的技术，用于无创记录高密度的神经元动力学 时空分辨率，为神经科学领域提供了一个非常需要的工具。

Project Summary/Abstract The investigation of the complex neural dynamics and the cognitive functions of the brain requires non- invasive recording tools with high spatial and temporal resolution. Fluorescence imaging/microscopy is one of the state-of-the-art technologies for high spatial resolution recording of the activity of neuron populations. However, existing fluorescence neural imaging technologies generally have limited speed, providing less than a few hundred frames per second (or several milliseconds temporal resolution). This is not only limited by the technology barriers (e.g. the low speed of cameras and/or beam scanners), but also constrained by the low signal level emitted by the delicate micro-scale neuronal structures. The milliseconds or slower temporal resolution substantially precludes measuring the precise timing of the generation and propagation of neuron spikes, which is the key component of neural signaling. During this R&D program, Physical Sciences Inc. (PSI), Dartmouth College, and the Broad Institute of MIT and Harvard propose to develop and demonstrate a novel fluorescence neural imaging technology that enables high-speed recording of membrane potentials from multiple neurons. This technology combines two complementary imaging channels to achieve parallel neuronal recording with both sub-micron spatial and sub-millisecond temporal resolution. The high-speed recording function is achieved using a novel imaging technique based on a high-sensitivity single-point detector and a high-speed spatial light modulator (SLM). During the Phase I, we demonstrated the feasibility of the technology by imaging cultured neurons labeled with calcium and voltage indicating fluorescent sensors. During the proposed Phase II, we will upgrade the technology and further demonstrate its value in neuroscience investigations. The Phase II prototypes will include a universal high spatiotemporal resolution sensor that is compatible with various imaging setups including head-mounted fluorescence mini-microscopes. Two Phase II prototypes will be delivered to collaborating institutes for performance testing. The testing experiments will focus on demonstrating high spatiotemporal resolution recording of fast action potentials from both neuron somas in the brain in vivo and sub-cellular structures (e.g., dendrites and synapses) of neuron cultures or brain slices using genetically encoded voltage sensors. This R&D project will result in a robust technology for non-invasive recording of neuronal kinetics with high spatiotemporal resolution, offering a greatly needed tool in the neuroscience field.