A fully biological platform for monitoring mesoscale neural activity

用于监测中尺度神经活动的全生物平台

• 批准号: 9764377
• 负责人: Kafui Dzirasa
• 金额: $ 22.94万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9764377
• 关键词: 3-Dimensional; Address; Animal Model; Animals; Area; Autologous; Axon; Binding; Biocompatible Materials; Biological; Biomedical Engineering; Blood Vessels; Brain; Cells; Connexins; Dendritic Spines; Development; Dimensions; Discrimination; Electrical Synapse; Electrodes; Fibrosis; Future; Geometry; Glass; Gold; Graph; Growth; Human; Image; Implant; Implanted Electrodes; Individual; Light; Longevity; Metals; Methods; Modeling; Monitor; Mutagenesis; Neurons; Optics; Peripheral; Protein Engineering; Proteins; Research Personnel; Resolution; Sampling; Signal Transduction; Site; Spinal Ganglia; Structure; Surface; Techniques; Technology; Time; Tissues; Validation; Vertebrates; Work; angiogenesis; awake; base; brain tissue; cell type; design; high risk; human model; in vivo; metallicity; microendoscope; miniaturize; nanoscale; neuronal cell body; new technology; novel; optical imaging; relating to nervous system; sensor; tool

A fully biological platform for monitoring mesoscale neural activity One of the barriers to understanding the human brain is due to its geometry. Accessing brain tissue at single cell resolution has classically involved implanting electrodes (metallic or optical) directly into the brain. For deep subcortical structures, these approaches result in tissue destruction across the shallow brain areas that must be traversed to access deeper targets. Thus, classic approaches are fundamentally unable to allow concurrent sampling of activity from healthy fully intact tissue at all sites of the brain. While many novel technologies that exploit miniaturized nanoscale recording electrodes will increase number of single cells that can be recorded concurrently in the same brain, these approaches do not address the challenge raised by the geometry of the brain. We intend to develop a new technology to ‘functionally’ change the geometry of the brain by biologically projecting neural activity onto a flat surface outside of the brain. This ‘biological electrode’ will allow for the concurrent acquisition of single cell activity from all depths of fully intact brain tissue in awake-behaving animals. Furthermore, this technology will offer several advantages over currently available approaches: 1) Unlike metallic recording electrodes which induce fibrosis at the metal-brain interface and ultimately diminish signal quality, the fully biological electrode will allow investigators to stably monitor brain activity throughout the entire lifespan of model organisms; 2) The biological patch will utilize engineered proteins to form physical connections with target cell types. Thus, this technology will rival gold-standard in vivo intracellular recording approaches such as glass-pipette patching; 3) Since the engineered proteins that form the physical connections between the biological electrode and target cells can be targeted to individual cellular compartments, the biological patch will allow neural activity to be directly acquired from the soma, dendritic spines, and/or axons of single cells in a cell type specific manner; 4) Finally, the biological patch will be readily scalable to allow for recordings from 100,000s of single cells simultaneously. Thus, successful completion of this high-risk project will revolutionize neural recordings across model species and humans.

用于监测中尺度神经活动的全生物平台 理解人脑的障碍之一是其几何形状。访问 单细胞分辨率的脑组织通常涉及植入电极（金属或 光学）直接进入大脑。对于深层皮层下结构，这些方法会导致组织 破坏浅层大脑区域，必须穿过这些区域才能到达更深的目标。 因此，经典方法从根本上无法允许对活动进行并发采样 大脑所有部位的健康、完整的组织。虽然许多新技术利用 微型纳米级记录电极将增加可记录的单细胞数量 在同一大脑中同时记录，这些方法并不能解决所提出的挑战 通过大脑的几何形状。 我们打算开发一种新技术来“功能性”改变大脑的几何形状 通过生物学将神经活动投射到大脑外部的平坦表面上。这种“生物 “电极”将允许同时采集各个深度的单细胞活动 清醒动物的完整脑组织。此外，该技术将提供多种 与当前可用方法相比的优点：1）与金属记录电极不同，金属记录电极 诱导金属-脑界面纤维化并最终降低信号质量， 生物电极将使研究人员能够在整个过程中稳定地监测大脑活动 模式生物的寿命； 2) 生物贴片将利用工程蛋白质形成 与目标细胞类型的物理连接。因此，该技术将与体内黄金标准相媲美 细胞内记录方法，例如玻璃移液管修补； 3）由于设计 形成生物电极和靶细胞之间物理连接的蛋白质可以 针对单个细胞区室，生物贴片将允许神经活动 直接从细胞类型中单个细胞的体细胞、树突棘和/或轴突获得 具体方式； 4）最后，生物补丁将很容易扩展以允许记录 同时从 100,000 个单细胞中提取。至此，这次高风险的工作顺利完成 该项目将彻底改变模型物种和人类的神经记录。