Holographic Optics Technology Core

双光子模式化光遗传学激发是一种强大的新兴工具， 具有细胞精确性和特异性的活性。然而，用于双光子图案化的当前技术 体内照射靶向有限数量的具有相对较差的时间分辨率的神经元， 在大脑区域得到验证，尚未报道驱动哺乳动物的行为反应。的 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， 推进团队的光学硬件、软件和光遗传学能力。这些进步将使 双光子光遗传学刺激，以实现行为中的鲁棒和精确的分布式神经控制 动物的大脑区域和细胞类型。这三个研究项目都将与技术核心合作， 利用核心实验室在先进光学技术方面的独特专业知识， 雕刻激光波阵面，在不同的感觉区域询问具有单神经元分辨率的脑回路， 啮齿动物的大脑 首先，技术核心将整合和验证全光学成像和图案化的最佳实践。 双光子微扰、实验管理软件和光敏探针。这些国家的- 艺术工具将在整个团队中传播。下一步，核心将推进和优化特异性， 通过探索新的光学、算法和探针靶向解决方案， 为了提高刺激特异性和鲁棒性，新的硬件和光学设计， 横向和轴向维度上的可访问刺激场，以及用于大脑运动的闭环软件 赔偿最后，该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）和高脉冲能量刺激 激光，并通过精确地同步光学扰动与行为事件和与固有的 电动力学 通过以前所未有的时间分辨率（低于10 ms）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 目的是阐明大群神经元的合作活动如何驱动行为。优化 光学系统、软件系统和探头的集成将是跨 感觉形态我们的建议的一个独特优势是，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长， 问题解决是由实验相关的关注驱动的。

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.