3D-Fast Optical Interface for Rapid Volumetric Neural Sensing and Modulation

项目摘要 为了加深我们对神经回路功能的理解，需要新的工具来收集 来自参与共同神经计算的大量神经元的同时测量和 提供精确的功能调节。清醒动物表达钙指示剂的光学成像 提供来自局部神经回路内单个神经元的实时功能和空间信息。这个 目前成像技术的局限性包括覆盖单一大脑区域的小视野，以及 头部固定的要求，防止自然主义行为。此外，大多数光学成像 系统不允许同时进行高分辨率功能成像和空间局部化 光遗传调制。 为了迎接这一挑战，我们建议开发一种能够快速、实时地 体积神经记录和精确的光学刺激。通过配对微图案化LED的微型阵列 发射器具有轴向聚焦能力的电润湿透镜技术，我们将实现双工 记录和刺激数以千计的神经元。通过使用新型3D打印脚手架， 我们将能够创建模块化、可扩展、可定制的镜头阵列，允许大规模记录 用于神经回路的闭环调制的双向神经接口。我们将创建3D-FAST设备 通过在3D打印脚手架中组装模块化光学元件。最初的设备将在 麻醉的小鼠在呈现视觉刺激的过程中。光遗传刺激将被用来偏向 电路功能。 总而言之，这些实验将展示3D-FAST技术的独特能力。又快又高- 来自一定体积组织的钙瞬变的分辨率成像将与空间受限的光配对 用于光发生神经调制的递送。光学成像特性将与地面真实情况进行比较 双光子显微镜，以及神经调节的功能后果将通过电路进行解剖 调制。3D-FAST工具将带来新的功能来测量和调节 为了更好地理解行为背后的神经计算。另外，这个机构 将为未来完全可植入的光学记录和调制单元的开发奠定基础 用于自由移动、不受束缚的自然主义行为实验。

Project Summary To further our understanding of the function of neural circuits, there is a need for new tools that can collect simultaneous measurements from large populations of neurons involved in a common neural computation and provide precise functional modulation. Optical imaging in awake animals expressing calcium indicators provides real-time functional and spatial information from individual neurons within local neural circuits. The limitations of current imaging technology include small fields of view encompassing single brain regions, and the requirement for head fixation, which prevents naturalistic behavior. In addition, most optical imaging systems do not allow for simultaneous high-resolution functional imaging in combination with spatially-localized optogenetic modulation. To meet this challenge, we propose to develop an optical device (`3D-FAST') that allows for rapid, real-time volumetric neural recording and precise optical stimulation. By pairing miniature arrays of micropatterned LED emitters with the axial focusing capabilities of electrowetting lens technologies, we will achieve duplex recording and stimulation of many thousands of neurons. Through utilization of novel 3D-printed scaffolding, we will be able to create modular, expandable, customizable lens arrays that allow for recording of large-scale bi-directional neural interfaces for closed-loop modulation of neural circuits. We will create the 3D-FAST device through assembly of modular optical elements in a 3D-printed scaffolding. The initial device will be tested in in the anesthetized mouse during the presentation of visual stimuli. Optogenetic stimulation will be used to bias circuit function. In sum, these experiments will demonstrate the unique capabilities of the 3D-FAST technology. Rapid, high- resolution imaging of calcium transients from a volume of tissue will be paired with spatially-restricted light delivery for optogenetic neural modulation. The optical imaging properties will be compared with ground-truth two-photon microscopy, and the functional consequence of neuromodulation will be dissected through circuit modulation. The 3D-FAST tool will bring novel capabilities to measuring and modulating large populations of neurons in animals, to better understand the neural computations that underlie behavior. In addition, this body of work will lay the ground for future development of fully implantable optical recording and modulating units for use in freely-moving, untethered naturalistic behavior experiments.