Supplemental support for the development of high spatiotemporal resolution neuronal imager

对高时空分辨率神经元成像仪开发的补充支持

• 批准号: 10879866
• 负责人: Youbo Zhao
• 金额: $ 39.89万
• 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/10879866
• 关键词: Acceleration; Action Potentials; Administrative Supplement; Brain; Calcium; Collaborations; Complex; Dendrites; Development; Fluorescence; Generations; Head; Human; Image; Imaging technology; Investigation; Kinetics; Label; Light; Measures; Membrane Potentials; Mental disorders; Microscope; Microscopy; Neurons; Neurosciences; Neurosciences Research; Phase; Population; Process; Research; Resolution; Signal Transduction; Slice; Speed; Structure; Subcellular structure; Synapses; Technology; Testing; cognitive function; college; commercialization; cost; detector; experimental study; fluorescence imaging; imager; improved; in vivo; millisecond; nervous system disorder; neural; neuroimaging; neuronal cell body; neurotransmission; novel; novel imaging technique; performance tests; physical science; programs; prototype; research and development; sensor; spatiotemporal; submicron; temporal measurement; tool; voltage

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. During an administrative supplement support, additional sensors will be built for demonstrations to key opinion leaders, which will accelerate the commercialization process of the technology. 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.

项目总结/摘要 复杂的神经动力学和大脑的认知功能的调查需要非- 具有高空间和时间分辨率的侵入性记录工具。荧光成像/显微镜是一种 高空间分辨率记录神经元群体活动的最新技术。 然而，现有的荧光神经成像技术通常具有有限的速度，提供较少的 每秒几百帧（或几毫秒的时间分辨率）。这不仅限于 受技术障碍（例如，相机和/或光束扫描仪的低速）的限制，但也受到以下因素的限制： 由精细的微观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测量产生和传播的精确定时 这是神经信号的关键组成部分。在这个研发项目中， 物理科学公司(PSI)，达特茅斯学院，麻省理工学院和哈佛大学的布罗德研究所建议 开发和展示一种新的荧光神经成像技术， 记录来自多个神经元的膜电位。这项技术结合了两个互补的 成像通道，以实现亚微米空间和亚毫秒的并行神经元记录 时间分辨率高速记录功能是使用一种新的成像技术， 高灵敏度单点探测器和高速空间光调制器（SLM）。在第一阶段， 我们通过对用钙标记的培养神经元进行成像， 电压指示荧光传感器。在建议的第二期工程中，我们会提升技术， 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个通用的 高时空分辨率传感器，其与包括头戴式 微型荧光显微镜第二阶段的两个原型将交付给合作研究所， 性能测试。测试实验将集中于展示高时空分辨率 记录体内脑内神经元胞体和亚细胞结构的快速动作电位 (e.g.,树突和突触）。 在行政补充支持期间，将建造更多的传感器，用于演示关键 意见领袖，这将加速该技术的商业化进程。该研发项目将 导致用于非侵入性记录神经元动力学的鲁棒技术， 分辨率，提供了一个非常需要的工具，在神经科学领域。