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

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

展开

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.

项目摘要在每个大脑区域内，神经元可以分为数十种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，并且对疾病状态产生了独特的影响。传统上，体内电生理记录对我们对行为神经元基础的理解做出了宝贵的贡献，无法区分遗传定义的细胞类型的活性。尽管我们仅仅简单地从许多神经元中测量动作电位的能力取得了进步，但仍然很难将这些尖峰列车连接到潜在的细胞类型，以及有关其形态，连通性模式和内在特性所知的所有知识。在这里，我们建议通过创建能够具有高密度电生理记录和多色光输送的这些问题的版本来扩展广泛使用的神经质子平台。该设备称为Neuropixels Opto，可用于通过称为“ Optotaging”的方法来识别细胞类型，同时还支持对遗传定义的神经种群的精确操纵。我们将与IMEC合作，IMEC是一家纳米电子研发组织，可独家访问世界一流的制造设施，设计和制造具有1280个电气读数站点的完全集成的可植入录音设备，最多48个红光发射器，以及最多62个蓝色的蓝光发射器。该探针的概念验证版本已经交付给艾伦学院，在该研究所成功使用了该研究所。但是，开发可以大规模制造并以探测器约2500美元售出的设备需要更多的工作，以促进其在整个系统神经科学社区中的传播。通过与三个外部测试站点合作，我们将验证神经质子光学的效率，以在四个大脑区域进行细胞类型的记录和操纵：视觉皮层，内嗅皮层，纹状体，纹状体和腹侧段段区域。此外，我们将通过开发用于控制这些问题的模块来扩展流行的数据采集软件包，并创建新的转基因鼠标线条，使用户可以更简单地执行双色光遗传学操纵。综上所述，这些努力将使神经质子光Opto成为理解不同细胞类型在活体大脑中的作用的功能强大，易于访问且必不可少的工具。