High Spatiotemporal Resolution Neural Recording System Using Active Sensing

使用主动传感的高时空分辨率神经记录系统

• 批准号: 10591614
• 负责人: Youbo Zhao
• 金额: $ 87万
• 依托单位: PHYSICAL SCIENCES, INC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10591614
• 关键词: Action Potentials; Animals; Architecture; Brain; Calcium; Collaborations; Complex; Computer software; Data; Data Collection; Dedications; Dendrites; Detection; Devices; Electrophysiology (science); Engineering; Feedback; Fiber; Fluorescence; Future; Generations; Head; Human; Image; Imaging Device; Imaging technology; In Vitro; Investigation; Kinetics; Label; Laboratory Research; Light; Marketing; Measures; Membrane Potentials; Mental disorders; Microscope; Microscopy; Neurons; Neurosciences; Neurosciences Research; Noise; Optics; Performance; Phase; Population; Preparation; Publishing; Research; Resolution; Scientist; Signal Transduction; Slice; Speed; Structure; Subcellular structure; Synapses; System; Technology; Test Result; Testing; Universities; Update; Wisconsin; brain based; brain research; cognitive function; college; commercialization; cost; data reduction; design; detector; electronic sensor; experimental study; fluorescence imaging; imager; imaging approach; improved; in vivo; innovation; instrument; interest; meter; millisecond; multidisciplinary; nervous system disorder; neural; neural network; neuroimaging; neuronal cell body; neurotransmission; novel; novel imaging technique; operation; optical imaging; performance tests; physical science; programs; prototype; quasar; research and development; sensor; spatiotemporal; submicron; success; temporal measurement; tool; voltage; voltage sensitive dye

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.

项目概要/摘要 对复杂的神经动力学和大脑认知功能的研究需要非 具有高空间和时间分辨率的侵入性记录工具。荧光成像/显微镜是其中之一 用于高空间分辨率记录神经元群活动的最先进技术。 然而，现有的荧光神经成像技术普遍速度有限，提供的信息较少 每秒几百帧（或几毫秒时间分辨率）。这不仅是有限的 受到技术障碍（例如相机和/或光束扫描仪的低速）的限制，但也受到限制 精致的微型神经元结构发出的低信号水平。毫秒或更慢 时间分辨率基本上妨碍了测量生成和传播的精确时间 神经元尖峰是神经信号传导的关键组成部分。在此研发计划期间，物理 Sciences Inc. (PSI)、达特茅斯学院以及麻省理工学院和哈佛大学布罗德研究所提议 开发并展示一种新型荧光神经成像技术，可实现高速 记录多个神经元的膜电位。该技术结合了两种互补的技术 成像通道实现亚微米空间和亚毫秒并行神经元记录 时间分辨率。高速记录功能是使用基于新型成像技术实现的 在高灵敏度单点探测器和高速空间光调制器（SLM）上。在第一阶段期间， 我们通过对钙标记的培养神经元进行成像来证明该技术的可行性 电压指示荧光传感器。在拟议的第二阶段，我们将升级技术并 进一步证明其在神经科学研究中的价值。第二阶段原型将包括一个通用的 高时空分辨率传感器，兼容各种成像设置，包括头戴式 荧光微型显微镜。两个二期原型将交付给合作机构 性能测试。测试实验将重点展示高时空分辨率 记录体内大脑神经元体和亚细胞结构的快速动作电位 使用基因编码电压传感器的神经元培养物或脑切片（例如树突和突触）。 该研发项目将带来一种强大的技术，用于非侵入性记录神经元动力学，具有高 时空分辨率，为神经科学领域提供了急需的工具。