NeuroNex Technology Hub: Multimodal Integrated Neural Technologies (MINT) - Connecting Physiology to Functional Mapping

NeuroNex 技术中心：多模态集成神经技术 (MINT) - 将生理学与功能映射联系起来

• 批准号: 1707316
• 负责人: Euisik Yoon
• 金额: $ 310万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Cooperative Agreement
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1707316&HistoricalAwards=false
• 关键词: NeuroNex; Technology; Hub; Multimodal; Integrated

In order to understand how neural signals propagate to conduct specific functions in behaving animals and how individual neurons are physically connected in the context of behavior, advanced tools should be available at the hands of neuroscientists. The Multimodal Integrated Neural Technologies (MINT) hub aims to develop and provide tools that are able to read from and modulate neurons at multiple sites independently at high spatial and temporal resolutions. The hub will disseminate tools and methods to correlate the recorded cell activity with the structural connection. In this way, the connectivity of active cells can be visualized, labeled, and traced for detailed functional mapping. The mission of the MINT hub is to provide a collection of tools, synergistically developed, integrated, and available to the neuroscience community, to address one theme: connecting neurophysiology and structural analysis with a greater scale and resolution. The synergistic integration of these neurotechnology tools at the MINT Hub would accelerate the rate of discovery in neuroscience. This in turn can be expected to pave the way to improved treatments for neurological disorders and to breakthroughs in artificial intelligence, especially neuromorphic computing. The MINT hub will provide annual training workshops for new users to be familiar with new technologies and able to use them effectively. To achieve sustainability, the hardware tools will be actively marketed to the community and those with sustainable volume will be transitioned to commercialization partners. Importantly, this program will cross-train neuroscience and technology personnel during the course of this program, resulting in preparation of a new generation of multi-disciplinary engineers and scientists.This hub uniquely combines high-density electrodes, chemical sensing, optical stimulation, and cell labeling. Fiberless high-density optoelectrodes can allow optical stimulation of individual or few neurons with high specificity and selectivity using monolithically integrated micro-LEDs or optical waveguides on multi-shank silicon probes. Carbon microthreads will be used to create advanced arrays that will dramatically increase the ability to record from interconnected neurons and label those cells with high accuracy. Advanced metal alloys will also be used to greatly enhance the signal-to-noise ratio of miniaturized electrodes. The MINT hub will innovate viral vector delivery and tissue clearing in the nervous system and combine these with multispectral labeling for intact cell phenotyping. Furthermore, an open-source software will be developed to improve the accuracy and efficiency of anatomical reconstruction for creating connectivity maps. The MINT hub will validate the developed tools and methods in three in-vivo experiments to exemplify what can be accomplished when the proposed modalities and methods are synergistically integrated. This NeuroTechnology Hub award is co-funded by the Division of Emerging Frontiers within the Directorate for Biological Sciences, and the Division of Chemical, Bioengineering, Environmental & Transport Systems within the Directorate for Engineering as part of the BRAIN Initiative and NSF's Understanding the Brain activities.

为了了解神经信号如何传播以执行动物行为中的特定功能，以及单个神经元如何在行为背景下进行物理连接，神经科学家应该提供先进的工具。多模式集成神经技术(MINT)中心旨在开发和提供能够以高空间和时间分辨率独立读取和调制多个地点的神经元的工具。该中心将传播工具和方法，将记录的细胞活动与结构连接联系起来。通过这种方式，可以可视化、标记和跟踪活动细胞的连接性，以获得详细的功能图。MINT中心的使命是提供一系列工具，协同开发、集成并可供神经科学界使用，以解决一个主题：以更大的规模和分辨率将神经生理学和结构分析联系起来。这些神经技术工具在薄荷中心的协同整合将加快神经科学的发现速度。这反过来有望为神经疾病的改进治疗铺平道路，并为人工智能，特别是神经形态计算的突破铺平道路。铸币中心将为新用户提供年度培训讲习班，以熟悉新技术并能够有效地使用它们。为了实现可持续发展，硬件工具将积极向社区销售，那些具有可持续数量的工具将过渡到商业化合作伙伴。重要的是，该项目将在该项目过程中交叉培训神经科学和技术人员，从而培养新一代多学科的工程师和科学家。这个中心独特地结合了高密度电极、化学传感、光学刺激和细胞标记。无光纤高密度光电极可以使用单片集成的微型LED或多柄硅探针上的光波导对单个或少数神经元进行高特异性和选择性的光刺激。碳微线将被用来创造先进的阵列，这将极大地提高从相互连接的神经元进行记录并高精度标记这些细胞的能力。先进的金属合金也将被用来大大提高小型化电极的信噪比。薄荷中心将创新神经系统中的病毒载体传递和组织清除，并将这些与多光谱标记相结合，以进行完整的细胞表型鉴定。此外，还将开发一个开源软件，以提高创建连接图的解剖重建的准确性和效率。薄荷中心将在三个体内实验中验证开发的工具和方法，以例证当建议的模式和方法协同集成时可以实现的结果。该神经技术中心奖由生物科学局新兴前沿部门和工程局化学、生物工程、环境和运输系统部门共同资助，作为大脑倡议和NSF了解大脑活动的一部分。

项目成果

Systemic AAV vectors for widespread and targeted gene delivery in rodents

• DOI: 10.1038/s41596-018-0097-3
• 发表时间: 2019-02-01
• 期刊: NATURE PROTOCOLS
• 影响因子: 14.8
• 作者: Challis, Rosemary C.;Kumar, Sripriya Ravindra;Gradinaru, Viviana
• 通讯作者: Gradinaru, Viviana

Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates.

• DOI: 10.1038/s41467-023-38582-7
• 发表时间: 2023-06-08
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Chen, Xinhong;Wolfe, Damien A.;Bindu, Dhanesh Sivadasan;Zhang, Mengying;Taskin, Naz;Goertsen, David;Shay, Timothy F.;Sullivan, Erin E.;Huang, Sheng-Fu;Kumar, Sripriya Ravindra;Arokiaraj, Cynthia M.;Plattner, Viktor M.;Campos, Lillian J.;Mich, John K.;Monet, Deja;Ngo, Victoria;Ding, Xiaozhe;Omstead, Victoria;Weed, Natalie;Bishaw, Yeme;Gore, Bryan B.;Lein, Ed S.;Akrami, Athena;Miller, Cory;Levi, Boaz P.;Keller, Annika;Ting, Jonathan T.;Fox, Andrew S.;Eroglu, Cagla;Gradinaru, Viviana
• 通讯作者: Gradinaru, Viviana

Engineered AAVs for non-invasive gene delivery to rodent and non-human primate nervous systems.

• DOI: 10.1016/j.neuron.2022.05.003
• 发表时间: 2022-07-20
• 期刊: NEURON
• 影响因子: 16.2
• 作者: Chen, Xinhong;Kumar, Sripriya Ravindra;Adams, Cameron D.;Yang, Daping;Wang, Tongtong;Wolfe, Damien A.;Arokiaraj, Cynthia M.;Ngo, Victoria;Campos, Lillian J.;Griffiths, Jessica A.;Ichiki, Takako;Mazmanian, Sarkis K.;Osborne, Peregrine B.;Keast, Janet R.;Miller, Cory T.;Fox, Andrew S.;Chiu, Isaac M.;Gradinaru, Viviana
• 通讯作者: Gradinaru, Viviana

An update to Hippocampome.org by integrating single-cell phenotypes with circuit function in vivo.

• DOI: 10.1371/journal.pbio.3001213
• 发表时间: 2021-05
• 期刊: PLoS biology
• 影响因子: 9.8
• 作者: Sanchez-Aguilera A;Wheeler DW;Jurado-Parras T;Valero M;Nokia MS;Cid E;Fernandez-Lamo I;Sutton N;García-Rincón D;de la Prida LM;Ascoli GA
• 通讯作者: Ascoli GA

Artifact-free and high-temporal-resolution in vivo opto-electrophysiology with microLED optoelectrodes

• DOI: 10.1038/s41467-020-15769-w
• 发表时间: 2020-04-28
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Kim, Kanghwan;Voroslakos, Mihaly;Yoon, Euisik
• 通讯作者: Yoon, Euisik