Development of 3D-FAST Optical Interface for Rapid Volumetric Neural Sensing and Modulation

开发用于快速体积神经传感和调制的 3D-FAST 光学接口

基本信息

批准号：
10294019
负责人：
Emily Gibson
金额：
$ 266.58万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10294019
关键词：
3-Dimensional 3D Print Animals Behavior Behavioral Assay Brain Brain region Calcium Code Coupling Development Devices Electronics Elements Evaluation Feedback Functional Imaging Future Head Hippocampus (Brain)Image Imaging technology Individual Light Lighting Measurement Measures Membrane Microscopy Monitor Motion Movement Mus Neurons Neurophysiology - biologic function Noise Odors Optics Outcome Pattern Penetration Phase Population Presynaptic Terminals Resolution Rodent Role Scanning Series Signal Transduction Slice Structure Sum Techniques Technology Testing Time Tissues Variant awake basal forebrain calcium indicator cholinergic cholinergic neuron design detector electrical measurement experimental study hippocampal pyramidal neuron imaging properties imaging system improved in vivo insight lens motor learning multi-electrode arrays neural circuit neuroregulation novel optical imaging optogenetics prevent prototype relating to nervous system sample fixation scaffold spatiotemporal tissue phantom tool two photon microscopy vibration voltage way finding

项目摘要

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 or voltage 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 two versions of the 3D-FAST device. 3D-FAST-GECI that will provide fast, volumetric imaging at 30 Hz for GCaMP imaging, and 3D-FAST-GEVI that will provide frame rates of 1 kHz at a single plane combined with a slower, high resolution volume scan. Initially, the devices will be tested in the anesthetized, and then awake, freely moving mouse for experiments using GCaMP, voltage indicators ASAP and Voltron, and finally combining with localized optogenetics for closed loop feedback. In sum, these experiments will demonstrate the unique capabilities of the 3D-FAST technology. Rapid, imaging of improved voltage indicators will be paired with spatially-restricted light delivery for optogenetic neural modulation for the first time in a freely moving mouse. The optical imaging properties will be compared with ground-truth two-photon microscopy, and the functional consequence of neuromodulation will be dissected through behavioral assays. The 3D-FAST tool will bring novel capabilities to measuring and modulating large populations of neurons in freely-moving 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.

项目摘要为了进一步了解神经电路的功能，需要新工具可以从涉及的大量神经元中收集同时测量的共同神经计算并提供精确的功能调制。表达清醒动物的光学成像钙或电压指标提供了个人的实时功能和空间信息局部神经回路中的神经元。当前成像技术的局限性包括查看包含单个大脑区域以及对头部固定的要求，这可以防止自然行为。此外，大多数光学成像系统不允许同时高分辨率功能成像结合空间定位的光遗传学调制。为了应对这一挑战，我们建议开发一种光学设备（`3D-fast'），该设备可以快速，实现时间体积神经记录和精确的光学刺激。通过配对微型阵列微图案的LED发射器具有电动表镜头技术的轴向聚焦功能，我们将实现数千个神经元的双工记录和刺激。通过新颖的利用 3D打印的脚手架，我们将能够创建模块化，可扩展，可自定义的镜头阵列允许记录大规模双向神经界面，以进行神经的闭环调制电路。我们将创建两个版本的3D快速设备。 3D-fast-geci将提供快速，体积用于GCAMP成像的30 Hz成像和3D-FAST-GEVI，将在A处提供1 kHz的帧速率单个平面与较慢的高分辨率体积扫描结合在一起。最初，设备将在使用GCAMP，电压指示器进行麻醉，然后清醒，自由移动鼠标进行实验尽快和Voltron，最后与局部光遗传学结合，以进行封闭环反馈。总而言之，这些实验将证明3D快速技术的独特功能。迅速的，改进的电压指示器的成像将与空间限制的光输送配对在自由移动的小鼠中首次获得光遗传学神经调节。光学成像属性将与地面两光子显微镜进行比较，并将神经调节将通过行为分析进行解剖。 3D快速工具将带来新颖测量和调节自由移动动物中大量神经元种群的能力，以更好了解行为基础的神经计算。此外，这项工作将是未来开发完全可植入的光学记录和调节单元的理由自由移动的，不受限制的自然主义行为实验。