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.

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它的几何形状。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。对于深层皮质下结构，这些方法导致组织 破坏大脑浅层区域，必须穿过这些区域才能到达更深的目标。 因此，传统方法从根本上无法允许对活动进行并发采样， 健康完整的脑组织虽然许多新技术利用了 微型化的纳米级记录电极将增加可以被 同时记录在同一个大脑中，这些方法不能解决所提出的挑战， 大脑的几何形状。 我们打算开发一种新技术来“功能性地”改变大脑的几何形状 将神经活动投射到大脑外部的平面上。这是生物学上的 “电极”将允许从完全电刺激的所有深度同时采集单细胞活性。 清醒动物的完整脑组织。此外，该技术还将提供多个 与目前可用的方法相比的优点：1）与金属记录电极不同， 在金属-大脑界面诱导纤维化，并最终降低信号质量， 生物电极将允许研究人员在整个过程中稳定地监测大脑活动。 模式生物的寿命; 2）生物补丁将利用工程蛋白质形成 与目标细胞类型的物理连接。因此，这项技术将在体内与黄金标准相媲美 细胞内记录方法，如玻璃吸管修补; 3）由于工程化的 在生物电极和靶细胞之间形成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索马、树突棘和/或轴突获得 4）最后，生物补丁将易于扩展以允许记录 从10万个单细胞中分离出来因此，成功完成这一高风险 该项目将彻底改变模型物种和人类的神经记录。