All holographic two-photon electrophysiology

全全息双光子电生理学

基本信息

批准号：
10616937
负责人：
Hillel Adesnik
金额：
$ 407.69万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10616937
关键词：
3-Dimensional Acceleration Action Potentials Address Algorithms Animals BRAIN initiative Benchmarking Brain Calibration Cell Size Code Cognition Development Disease Electrophysiology (science)Engineering Esthesia Functional Imaging Health Heating Holography Image Lasers Light Lighting Measures Mediating Membrane Microscope Microscopy Monitor Morphologic artifacts Motion Neurons Neurosciences Research Opsin Optics Performance Population Process Resolution Sampling Scanning Shapes Source Speed Spottings System Technology Testing Time Update Writing computer generated imaging approach imaging platform in vivo light scattering microbial microscopic imaging millisecond neural neural network neural patterning neuroimaging neuroregulation new technology novel novel strategies optogenetics redshift scale up sensor spatiotemporal temporal measurement two-photon voltage yeast two hybrid system

项目摘要

PROJECT SUMMARY Achieving a detailed understanding of the neural codes of sensation, action, and cognition will require technologies that can both sample and perturb neural activity with millisecond precision and cellular resolution across large populations of neurons. We will develop an all-optical holographic two-photon microscope that can simultaneously record and perturb population neural activity with cellular resolution and millisecond precision. To achieve this, we will leverage multispectral temporally focused three-dimensional (3D) wavefront shaping. This new form of hybrid two-photon functional imaging will enable simultaneous illumination of user-defined ensembles of neurons in 3D with cell-size spots of two-photon excitation light at two different wavelengths – one for imaging a voltage sensor and one for controlling neural activity optogenetically. The two holographic optical paths will be completely independent and update at >kilohertz speed with the ability to sample and perturb the membrane voltage of tens to hundreds of neurons at a time. In tandem, we will develop task-optimized two-photon excitable red-shifted genetically encoded voltage sensors (GEVIs) and ultrapotent blue-shifted microbial opsins that are spectrally separable. The development of an all-holographic read/write microscope will permit neuronal recording and perturbation on spatial and temporal scales that are currently well beyond reach, which could substantially facilitate systems neuroscience research.

项目概要要详细了解感觉、动作和认知的神经编码，需要能够以毫秒精度和细胞分辨率对大量神经元进行采样和扰动的技术。我们将开发一种全光学全息双光子显微镜。可以以细胞分辨率和毫秒精度同时记录和扰动群体神经活动，为了实现这一目标，我们将利用多光谱时间聚焦三维（3D）波前整形来实现这种新形式的混合双光子功能成像。使用两种不同波长的双光子激发光的细胞大小点同时照明用户定义的 3D 神经元群 - 一种用于对电压传感器进行成像，另一种用于光遗传学控制神经活动这两个全息光路将完全独立。并以>千赫兹的速度进行更新，能够同时采样和扰动数十到数百个神经元的膜电压。同时，我们将开发任务优化的双光子可兴奋红移遗传技术。编码电压传感器（GEVI）和光谱可分离的超强蓝移微生物视蛋白全全息读/写显微镜的发展将允许在空间和时间尺度上进行神经元记录和扰动，这在很大程度上是遥不可及的。促进系统神经科学研究。