Neuropixels Opto: Integrated Silicon Probes for Cell-Type-Specific Electrophysiology

Neuropixels Opto：用于细胞类型特异性电生理学的集成硅探针

基本信息

批准号：
10731991
负责人：
Joshua H Siegle
金额：
$ 212.79万
依托单位：
ALLEN INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-18 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10731991
关键词：
Action Potentials Adoption Anatomy Area BRAIN initiative Behavior Brain Brain region Categories Cells Chronic Classification Cognition Collaborations Color Communities Complex Computer software Corpus striatum structure Data Development Devices Disease Electrodes Electrophysiology (science)Elements Enterobacteria phage P1 Cre recombinase FLP recombinase Genomics Goals Heating Human Implant Individual Laboratories Lead Light Link Measures Methods Molecular Monitor Morphology Mus Neurons Neurophysiology - biologic function Neurosciences Opsin Optics Pattern Perception Phase Play Population Positioning Attribute Process Property Reagent Reporter Research Personnel Role Signal Transduction Silicon Site Source System Taxonomy Technology Testing Time Tissues Training Transgenic Mice Transgenic Organisms Ventral Tegmental Area Viral Genes Visual Cortex Visualization Work advanced system brain cell cell type cost data acquisition density design efficacy validation entorhinal cortex experimental study extracellular fabrication flexibility genetic manipulation implantable device improved in vivo information processing light gated manufacture manufacturing cost manufacturing process millisecond miniaturize nanoelectronics neural neural circuit optogenetics prototype redshift research and development stability testing temporal measurement tool transgene expression

项目摘要

PROJECT SUMMARY Within every brain region, neurons can be classified into dozens or hundreds of different cell types, each with unique functional roles and unique impacts on disease states. Traditionally, in vivo electrophysiological recordings—which have made invaluable contributions to our understanding of the neural basis of behavior— have not been able to distinguish the activity of genetically defined cell types. Despite recent advances in our ability to measure action potentials from many neurons simultaneously, it remains difficult to connect these spike trains to underlying cell types and all that is known about their morphology, connectivity patterns, and intrinsic properties. Here, we propose to extend the widely used Neuropixels platform by creating a version of these probes that is capable of both high-density electrophysiological recording and multi-color light delivery. This device, called Neuropixels Opto, could be used to identify cell types through an approach known as “optotagging,” while also facilitating precise manipulations of genetically defined neural populations. We will work with IMEC, a nanoelectronics R&D organization with exclusive access to world-class fabrication facilities, to design and build a fully integrated implantable recording device with 1280 electrical readout sites, up to 48 red light emitters, and up to 62 blue light emitters. A proof-of-concept version of this probe has already been delivered to the Allen Institute, where it was successfully used in an optotagging experiment. However, more work is required to develop a device that can be manufactured at scale and sold for around $2500/probe, in order to facilitate its dissemination throughout the systems neuroscience community. In collaboration with three external test sites, we will validate the efficacy of Neuropixels Opto for performing cell-type-specific recordings and manipulations in four brain regions: the visual cortex, entorhinal cortex, striatum, and the ventral tegmental area. In addition, we will extend popular data acquisition packages by developing modules for controlling these probes, as well as create new transgenic mouse lines that make it much simpler for users to carry out dual-color optogenetic manipulations. Taken together, these efforts will make Neuropixels Opto a powerful, accessible, and indispensable tool for understanding the role that different cell types play in living brains.

项目概要在每个大脑区域内，神经元可以分为数十或数百种不同的细胞类型，每种细胞类型都具有独特的功能作用和对疾病状态的独特影响传统上，体内电生理记录为我们理解神经基础做出了宝贵贡献。尽管我们最近在同时测量许多神经元的动作电位的能力方面取得了进展，但仍无法区分基因定义的细胞类型的活动，但将这些尖峰序列与潜在的细胞类型以及所有关于它们的已知信息联系起来仍然很困难。形态、连接模式和内在属性。我们建议通过创建能够进行高密度电生理记录和多色光传输的探针版本来扩展广泛使用的 Neuropixels 平台，该设备称为 Neuropixels Opto，可用于通过一种方法识别细胞类型。我们将与拥有世界一流制造设施的纳米电子研发组织 IMEC 合作，设计和构建一个完整的神经网络。具有 1280 个电读出点、最多 48 个红光发射器和最多 62 个蓝光发射器的集成植入式记录设备已交付给艾伦研究所，并成功用于该研究所。然而，还需要做更多的工作来开发一种可以大规模生产并以每个探针 2500 美元左右的价格出售的设备，以促进其在整个系统神经科学界的传播。通过三个外部测试站点，我们将验证 Neuropixels Opto 在四个大脑区域（视觉皮层、内嗅皮层、纹状体和腹侧被盖区）执行细胞类型特异性记录和操作的功效。此外，我们还将扩展流行的区域。通过控制这些探针的模块开发数据采集包，以及创建新的转基因小鼠品系，使用户能够更轻松地进行双色光遗传学操作，总而言之，这些努力将使 Neuropixels 成为可能。 Opto 是一种强大、易于使用且不可或缺的工具，可用于了解不同细胞类型在活体大脑中所扮演的角色。