Holographic Optics Technology Core

全息光学技术核心

• 批准号: 10456140
• 负责人: Shy Shoham
• 金额: $ 85.31万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10456140
• 关键词: Action Potentials; Algorithms; Animals; Area; BRAIN initiative; Behavior; Behavioral; Brain; Cells; Code; Computer software; Development; Dimensions; Electrophysiology (science); Ensure; Event; Financial compensation; Goals; Grant; Head; Heart; Image; Individual; Laboratories; Lasers; Lateral; Light; Lighting; Methods; Modality; Morphologic artifacts; Motion; Movement; Mus; Neurons; Optics; Organ; Pattern; Physiologic pulse; Problem Solving; Radial; Reporting; Research; Research Personnel; Research Project Grants; Resolution; Rodent; Saccades; Sampling; Sensory; Smell Perception; Specificity; Speed; Stimulus; System; Technical Expertise; Techniques; Technology; Time; Vision; Work; awake; behavior measurement; behavioral response; cell type; design; experimental study; improved; in vivo; innovative technologies; millisecond; neural circuit; neuroregulation; novel; optical imaging; optogenetics; relating to nervous system; response; sensory stimulus; software systems; spatiotemporal; technology development; temporal measurement; tool; two-photon

Two-photon patterned optogenetic excitation is a powerful emerging tool for perturbing distributed neural activity with cellular precision and specificity. However, current techniques for two-photon patterned illumination in vivo target a limited number of neurons with relatively poor temporal resolution, have not been validated across brain areas, and have not yet been reported to drive mammalian behavioral responses. The Technology Core will tackle a set of technically advanced yet feasible dissemination and development steps, advancing the team’s optics hardware, software, and optogenetics capabilities. These advances will enable two-photon optogenetic stimulation to achieve robust and precise distributed neural control in behaving animals across brain areas and cell types. All three research projects will work with the Technology Core, leveraging the unique expertise of the core laboratories in advanced optical technologies that allow us to sculpt laser wavefronts to interrogate brain circuits with single-neuron resolution in different sensory regions of the rodent brain. First, the Technology Core will integrate and validate the best practices for all-optical imaging and patterned two-photon perturbation, experimental management software, and light-sensitive probes. These state-of-the- art tools will be disseminated across the team. Next, the core will advance and optimize the specificity and scale of patterned two-photon stimulation, by exploring new optical, algorithmic, and probe-targeting solutions for improving stimulation specificity and robustness, new hardware and optical designs for extending the accessible stimulation field in both lateral and axial dimensions, and closed-loop software for brain motion compensation. Finally, the core will advance and optimize the temporal precision of patterned two-photon stimulation using rate-optimized optogenetic probes, spatial light modulators (SLMs), and high pulse-energy lasers, and by accurately synchronizing the optical perturbations with behavioral events and with intrinsic electrical dynamics. By enabling the stimulation of hundreds of neurons with unprecedented (below 10 ms) temporal resolution in behaving animals across brain areas and cell types, the work of the Technology Core will enable the research objective of elucidating how the cooperative activity of large groups of neurons drives behavior. Optimization of optical systems, software systems, and probes will be a critical component of result comparisons across sensory modalities. A unique strength of our proposal is that the technical teams are involved in performing the in vivo experiments, ensuring that technical expertise is directly available during experiments and that the problem solving is driven by experimentally relevant concerns.

双光子图案光遗传学激发是扰动分布式神经网络的强大新兴工具 然而，目前的双光子图案化技术。 体内照明针对时间分辨率相对较差的有限数量的神经元，尚未得到证实 在整个大脑区域都得到了验证，并且尚未有报道称其可以驱动哺乳动物的行为反应。 技术核心将解决一系列技术先进但可行的传播和开发步骤， 提高团队的光学硬件、软件和光遗传学能力将成为可能。 双光子光遗传学刺激可实现稳健且精确的分布式神经控制行为 所有三个研究项目都将与技术核心一起工作， 利用先进光学技术核心实验室的独特专业知识，使我们能够 雕刻激光波前，以单神经元分辨率询问不同感觉区域的大脑回路 啮齿动物的大脑。 首先，技术核心将集成并验证全光学成像和图案化的最佳实践 双光子扰动、实验管理软件和光敏探针。 接下来，艺术工具将在整个团队中传播，核心将推进和优化特异性和功能。 通过探索新的光学、算法和探针靶向解决方案，实现图案化双光子刺激的规模 为了提高刺激特异性和鲁棒性，新的硬件和光学设计可扩展 横向和轴向均可触及的刺激场，以及用于大脑运动的闭环软件 最后，核心将提高和优化图案化双光子的时间精度。 使用速率优化的光遗传学探针、空间光调制器 (SLM) 和高脉冲能量进行刺激 激光，并通过将光学扰动与行为事件和固有的精确同步 电动力学。 通过以前所未有的（低于 10 毫秒）时间分辨率刺激数百个神经元 跨大脑区域和细胞类型的动物行为，技术核心的工作将使研究成为可能 目的是阐明大量神经元的协作活动如何驱动优化。 光学系统、软件系统和探头的集成将成为跨领域结果比较的关键组成部分 我们提案的独特优势在于技术团队参与执行。 体内实验，确保在实验过程中直接获得技术专业知识，并且 问题的解决是由实验相关的关注点驱动的。