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

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，同时识别其特定的细胞类型。特定的细胞类型在神经信息处理系统中具有精确的计算角色，但在大多数情况下，仅凭电活动无法识别细胞类型。在负责决策的皮质区域，混合的细胞类型带来的困难因层层、反复连接和大量的中间神经元类型而变得更加复杂。为了了解神经信息处理系统如何调节决策，有必要(1)从多个神经元同时记录以量化高维活动，(2)识别和确定这些集合中细胞类型的精确计算角色，以及(3)化学扰动神经集合以确定因果功能。该项目将首次同时启用所有这3个功能。建议的神经接口将包括记录电极、神经化学刺激器和扁平光学成像器波导，所有这些都在可植入微针的细小形状系数中。该装置将被用来研究与神经元群体活动有关的特定细胞类型的详细电路级功能。工程师和生物学家团队之间的合作为培养从事这一项目的研究生和本科生提供了一个独特的跨学科环境。PIS还将设计一门关于神经技术的新课程，向学生传授神经科学研究的需求和工程设计下一代神经接口的机会。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，以及基础神经生物学和基于光学标记的细胞转录图谱的进步，以阐明特定细胞类型在行为过程中神经元集体行动中的作用。研究人员将在最近开发的带有嵌入式微镜端口的基于聚合物的光波导平台的基础上，设计一种新型的平板成像器，该成像器可以与微电极单片集成，以光学方式成像细胞身份，同时记录细胞的电生理活动。建议的神经接口(I)紧凑而灵活，(Ii)将高密度电记录与化学刺激相结合，(Iii)包含电驱动的纳米复合聚合物，以及(Iv)使用基于对二甲苯聚合物光子波导的新型微成像器阵列实现杆上荧光成像。这一技术平台将用于研究大鼠在胡须刺激过程中编码感觉的细胞类型。开发的多模式探针还将传播到不同的神经生物学实验室，用于其他实验环境，以放大拟议项目的影响。这项跨领域研究的成果将是(I)一个新的技术平台，可以用来测试关于特定细胞类型在大脑中编码和转换信息的作用的各种神经科学假说，以及(Ii)一个有价值的数据集，它可以通过为仅基于电生理学的现有大规模数据增加新的维度来增强现有的神经元种群活动的数学模型，并将使一类全新的神经生物学实验成为可能。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.