Electrophysiological Maturation of Cerebral Organoids Correlates with Dynamic Morphological and Cellular Development. Electrophysiological Maturation of Cerebral Organoids Correlates with Dynamic Morphological and Cellular Development

Cerebral organoids (COs) are rapidly accelerating the rate of translational neuroscience based on their potential to model complex features of the developing human brain. Several studies have examined the electrophysiological and neural network features of COs; however, no study has comprehensively investigated the developmental trajectory of electrophysiological properties in whole-brain COs and correlated these properties with developmentally-linked morphological and cellular features. Here, we profiled the neuroelectrical activities of COs over the span of five months with a multi-electrode array (MEA) platform and observed the emergence and maturation of several electrophysiologic properties, including rapid firing rates and network bursting events. To complement these analyses, we characterized the complex molecular and cellular development that give rise to these mature neuroelectrical properties with immunohistochemical and single-cell transcriptomic analyses. This integrated approach underscores the value of COs as an emerging model system of human brain development and neurological disease. Overall design: Comparison of two organoid culture timepoints.

大脑类器官（Cerebral organoids, COs）因能够模拟发育中人脑的复杂特征，正快速推动转化神经科学的发展。已有多项研究探讨了大脑类器官的电生理与神经网络特征，但目前尚无研究全面探究全脑型大脑类器官电生理特性的发育轨迹，亦未将这些特性与发育相关的形态学及细胞特征建立关联。本研究借助多电极阵列（multi-electrode array, MEA）平台，对为期5个月的大脑类器官神经电活动进行了表征分析，观测到多项电生理特性的出现与成熟过程，包括高频放电与网络爆发事件。为补充上述分析，本研究通过免疫组织化学与单细胞转录组分析，对支撑上述成熟神经电特性的复杂分子与细胞发育过程进行了表征。这种整合研究方法凸显了大脑类器官作为新兴人脑发育与神经系统疾病模型体系的应用价值。整体设计：对比两类类器官培养时间节点。