NCS-FO:Collab:Multimodal sampling of neural ensembles: A high-density opto-electro-chemical neural interface for simultaneous electrical recording and optical imaging of cell-types

NCS-FO：协作：神经集合的多模态采样：高密度光电化学神经接口，用于同时对细胞类型进行电记录和光学成像

• 批准号: 1926756
• 负责人: Xinyan Cui
• 金额: $ 29.31万
• 依托单位: University of Pittsburgh
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1926756&HistoricalAwards=false
• 关键词: NCS; FO; Collab; Multimodal; sampling

This project develops novel devices and methods to record the electrical activity of large numbers of neurons while simultaneously identifying their specific cell types. Specific cell types have precise computational roles in neural information processing systems, but in most cases cell types are not identifiable from electrical activity alone. In cortical regions responsible for decision making, the difficulties posed by intermingled cell types are further complicated by layers, recurrent connections, and the multitude of interneuron types. In order to understand how neural information processing systems mediate decision making, it is necessary to (1) record simultaneously from many neurons to quantify high-dimensional activity, (2) identify and ascertain the precise computational roles of the cell types within those ensembles, and (3) chemically perturb neural ensembles to determine causal functionality. This project will for the first time enable all 3 of these capabilities simultaneously. The proposed neural interface will incorporate recording electrodes, neurochemical stimulators, and flat optical imager waveguides all in the slim form factor of an implantable micro-needle. This device will be used to study the detailed circuit-level functionality of specific cell types involved in the population activity of neurons. The collaboration between a team of engineers and biologists provides a unique interdisciplinary environment for training graduate and undergraduate students working on this project. The PIs will also design a new course on neurotechnology to teach students about the needs in neuroscience research and opportunities in engineering to design next generation neural interfaces. This project incorporates an integrative approach based on innovations in technology (nanotechnology, photonics, and neurotechnology) as well as advancements in fundamental neurobiology and transcriptional profiling of cells based on optical tagging to shed light on the role of specific cell types on collective actions of neurons during behavior. Building on a recently developed polymer-based optical waveguide platform with embedded micromirror ports, the investigators will design a novel flat imager that can be monolithically integrated with micro-electrodes to optically image the cell identities, while simultaneously recording their electrophysiology activity. The proposed neural interface (i) is compact and flexible, (ii) combines high-density electrical recording with chemical stimulation, (iii) contains electrically actuated nanocomposite polymers, and (iv) enables on-shank fluorescent imaging using a novel micro-imager array based on parylene polymer photonic waveguides. The utility of this technology platform will be demonstrated for studying cell types involved in encoding sensory sensations in rats during whisker stimulation. The developed multimodal probes will also be disseminated to different neurobiology labs to be used in other experimental contexts to amplify the impact of the proposed project. The outcome of this cross-field research will be (i) a new technology platform that can be used to test various neuroscience hypotheses on the role of specific cell types in encoding and transforming information in brain and (ii) a valuable dataset that can enhance existing mathematical models of neuronal population activity by adding new dimensions to the existing large-scale data based solely on electrophysiology, and will enable an entirely new class of neurobiology experiments.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该项目开发了新的设备和方法来记录大量神经元的电活动，同时识别其特定细胞类型。特定的细胞类型在神经信息处理系统中具有精确的计算作用，但是在大多数情况下，单独的电活动无法识别细胞类型。在负责决策的皮质区域中，层，复发连接和多种中间神经元类型所带来的困难更加复杂。为了了解神经信息处理系统如何介导决策，必须（1）（1）同时记录许多神经元以量化高维活动，（2）识别和确定这些结合体内细胞类型的精确计算作用，以及（3）化学上扰动神经结合物以确定因果功能。该项目将首次同时启用所有这些功能。所提出的神经界面将结合记录电极，神经化学刺激剂和平坦的光学成像仪在植入式微针的纤细外形中均匀地向导。该设备将用于研究神经元种群活性的特定细胞类型的详细电路级功能。一组工程师与生物学家之间的合作为培训该项目的培训研究生和本科生提供了独特的跨学科环境。 PI还将设计一门有关神经技术的新课程，以向学生传授神经科学研究的需求以及工程学的设计下一代神经界面的需求。该项目结合了一种基于技术创新（纳米技术，光子学和神经技术）的综合方法，以及基本神经生物学和细胞基本神经生物学和转录分析的进步，基于光学标记，基于光标记，以阐明在行为过程中特定细胞类型的作用。研究人员将建立在具有嵌入式微骨端口的最近开发的基于聚合物的光学波导平台的基础上，将设计一种新型的平坦成像仪，可以与微电极单层整合，以光学地对细胞身份进行光学图像，同时记录其电生理学活性。所提出的神经界面（I）是紧凑且柔性的，（ii）将高密度电记录与化学刺激结合在一起，（III）包含电动纳米复合材料聚合物，并且（IV）使用基于Parylene Parylene Polonics Polotonic波浪供应的新型微生物阵列在shank荧光成像上实现。该技术平台的实用性将被证明用于研究涉及晶须刺激过程中大鼠感觉感觉的细胞类型。开发的多模式探针也将被传播到不同的神经生物学实验室，以在其他实验环境中使用，以扩大所提出的项目的影响。 The outcome of this cross-field research will be (i) a new technology platform that can be used to test various neuroscience hypotheses on the role of specific cell types in encoding and transforming information in brain and (ii) a valuable dataset that can enhance existing mathematical models of neuronal population activity by adding new dimensions to the existing large-scale data based solely on electrophysiology, and will enable an entirely new class of neurobiology实验。该奖项反映了NSF的法定任务，并通过使用基金会的知识分子优点和更广泛的影响审查标准来评估值得支持。