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.

项目摘要 对感官，动作和认知的神经守则的详细理解需要一个技术，这些技术一次可以在多个大脑区域中一次扰动人口一个编码的每个主要维度。现有的控制系统无法完全应对这一挑战，因为它们是单向且空间尺度，速度或分辨率有限的。为了满足这一需求，我们将开发出一种全光努全息脑界面，该界面可以精确和双向改变大量组织和极高速度的神经种群活动。我们将构建和验证两色的两光子全息显微镜和介体显微镜，并优化单个转录双向光遗传学工具。利用一种新形式的超快速顺序全息照明，我们将获得细胞尺度，独立的双向控制，对跨脑组织的毫米毫米跨越数百万神经元的尖峰。最后，我们将开发在线方法，这些方法使用这种新系统来精确和有选择地操纵内源性内源性间相关性，神经尖峰时序和一次调整一个。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，而哪些只是偶然的。

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