Mesoscale bidirectional two-photon holographic optogenetics

中尺度双向双光子全息光遗传学

• 批准号: 10516934
• 负责人: Hillel Adesnik
• 金额: $ 317.68万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10516934
• 关键词: Address; Area; Automobile Driving; BRAIN initiative; Behavior; Brain; Code; Cognition; Color; Communities; Dimensions; Engineering; Esthesia; Goals; Interneurons; Lead; Lighting; Link; Mediating; Microscope; Monitor; Mus; Nervous system structure; Neurons; Neurosciences; Optics; Output; Pattern; Perception; Physiological; Population; Problem Solving; Resolution; Speed; System; Technology; Testing; Time; Tissues; Transcript; Update; awake; brain tissue; millimeter; millisecond; neural patterning; neurophysiology; neuroregulation; new technology; novel; novel strategies; optogenetics; prevent; rate of change; relating to nervous system; spatiotemporal; temporal measurement; theories; tool; two-photon; vector

PROJECT SUMMARY Achieving a detailed understanding of the neural codes of sensation, action, and cognition requires technologies that can causally perturb each of the major dimensions of population coding one at a time with extremely high precision across multiple brain areas. Existing control systems do not fully meet this challenge because they are unidirectional and have limited spatial scale, speed, or resolution. To address this need, we will develop an all-optical holographic brain interface that can precisely and bidirectionally alter neural population activity across large volumes of tissue and with extremely high speed. We will build and validate a two-color two-photon holographic microscope and mesoscope and optimize single transcript bidirectional optogenetic tools. Leveraging a new form of ultra-fast sequential holographic illumination, we will obtain cellular-scale, independent bidirectional control over the spiking of hundreds to thousands of neurons across millimeters of brain tissue. Finally, we will develop online approaches that use this new system to precisely and selectively manipulate endogenous interneuronal correlations, neural spike timing, and tuning one at a time. This new technology will allow neuroscientists to distinguish which features of the neural code are causal in neural computation and behavior and which are merely incidental.

项目概要 要详细了解感觉、行动和认知的神经编码，需要能够在多个大脑区域以极高的精度每次对群体编码的每个主要维度进行因果干扰的技术。现有的控制系统不能完全应对这一挑战，因为它们是单向的，并且空间尺度、速度或分辨率有限。为了满足这一需求，我们将开发一种全光学全息大脑接口，它可以以极高的速度精确地双向改变大量组织中的神经群体活动。我们将构建并验证双色双光子全息显微镜和介观镜，并优化单转录本双向光遗传学工具。利用一种新型的超快顺序全息照明，我们将获得细胞规模的、独立的双向控制，对数毫米脑组织中数百至数千个神经元的尖峰进行控制。最后，我们将开发在线方法，使用这一新系统来精确且有选择性地操纵内源性神经元间相关性、神经尖峰计时，并一次调整一个。这项新技术将使神经科学家能够区分神经代码的哪些特征在神经计算和行为中是因果关系，哪些只是偶然的。

项目成果

Cryo-EM structures of the channelrhodopsin ChRmine in lipid nanodiscs.

• DOI: 10.1038/s41467-022-32441-7
• 发表时间: 2022-08-17
• 期刊: Nature communications
• 影响因子: 16.6

Ultrafast light targeting for high-throughput precise control of neuronal networks.

• DOI: 10.1038/s41467-023-37416-w
• 发表时间: 2023-04-05
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Faini, Giulia;Tanese, Dimitrii;Molinier, Clement;Telliez, Cecile;Hamdani, Massilia;Blot, Francois;Tourain, Christophe;de Sars, Vincent;Del Bene, Filippo;Forget, Benoit C.;Ronzitti, Emiliano;Emiliani, Valentina
• 通讯作者: Emiliani, Valentina