Extracellular Recordings from Human Brain Organoids Using High-density CMOS Arrays

Human brain organoids replicate much of the cellular diversity and developmental anatomy of the human brain. However, the physiological behavior of neuronal circuits within organoids remains relatively under-explored. With high-density CMOS microelectrode arrays (26,400 electrodes) and shank electrodes (960 electrodes), we probed broadband and three-dimensional extracellular field recordings generated by spontaneous activity of human brain organoids. These recordings simultaneously captured local field potentials (LFPs) and single-unit activity extracted through spike sorting. From spiking activity, we estimated a directed functional connectivity graph of synchronous neural network activity, which showed a large number of weak functional connections enmeshed within a network skeleton of significantly fewer strong connections. Treatment of the organoid with a benzodiazepine induced a reproducible signature response that shortened the inter-burst intervals, increased the uniformity of the...人类脑类器官（human brain organoids）能够复现人脑绝大多数的细胞多样性与发育解剖结构。然而，类器官内神经元回路的生理行为仍相对缺乏系统性探索。本研究依托高密度CMOS微电极阵列（high-density CMOS microelectrode arrays，含26400个电极）与针状电极（shank electrodes，含960个电极），对人类脑类器官自发放电产生的宽频三维细胞外场电位开展了探测记录。此类记录可同时捕获局部场电位（local field potentials，LFPs），并通过尖峰分类（spike sorting）提取单单位活动（single-unit activity）。基于尖峰活动，我们构建了神经网络同步活动的有向功能连接图（directed functional connectivity graph），该图显示：大量弱功能连接交织于由数量显著更少的强连接构成的网络骨架中。使用苯二氮䓬类药物（benzodiazepine）处理类器官后，可诱导出可重复的特征响应：该响应缩短了爆发间隔（inter-burst intervals），提升了……