A fully biological platform for monitoring mesoscale neural activity

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因为它的几何形状。访问 在单细胞分辨率下，脑组织通常涉及植入电极(金属或 光学)直接进入大脑。对于皮质下深层结构，这些入路会产生组织 破坏浅层大脑区域，必须穿过这些区域才能接触到更深的目标。 因此，传统方法从根本上不能允许对来自 大脑所有部位的健康、完好的组织。虽然许多新技术利用了 小型化的纳米级记录电极将增加可以 同时记录在同一个大脑中，这些方法不能解决提出的挑战 通过大脑的几何形状。 我们打算开发一种新技术，从功能上改变大脑的几何形状 通过生物性地将神经活动投射到大脑外部的平面上。这是生物学的 电极将允许同时获取来自所有深度的单个细胞的活动 清醒动物的完整脑组织。此外，这项技术将提供几个 与目前可用的方法相比的优点：1)不同于金属记录电极 导致金属-大脑界面的纤维化，并最终降低信号质量，完全 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形成 与目标小区类型的物理连接。因此，这项技术将与体内的黄金标准相媲美 细胞内记录方法，如玻璃吸管贴片；3)自工程 在生物电极和靶细胞之间形成物理连接的蛋白质可以 这种生物贴片针对单个细胞隔间，将允许神经活动 直接从细胞体、树突棘和/或细胞类型中的单个细胞的轴突获得 具体的方式；4)最后，生物贴片将容易地扩展以允许记录 从100,000个单细胞同时开始。因此，成功完成这一高风险 该项目将使模式物种和人类的神经记录发生革命性变化。

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.