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 5 months with a multi-electrode array 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 gives rise to these mature neuroelectrical properties with immunohistochemical and single-cell transcriptomic analyses. This integrated approach highlights the value of COs as an emerging model system of human brain development and neurological disease.

脑类器官（COs）可以根据正在发展的人类大脑的复杂特征建模的潜力，迅速加快翻译神经科学的发展速度。有几项研究检查了CO的电生理和神经网络特征。然而，没有研究全面研究全脑COs的电生理特性的发展轨迹，并将这些特性与发育相关的形态和细胞特征相关联。在这里，我们使用多电极阵列平台分析了5个月内CO的神经电活动，并观察了几种电生理特性的出现和成熟，包括快速放电速率和网络爆裂事件。为了补充这些分析，我们通过免疫组织化学和单细胞转录组分析表征了复杂的分子和细胞发育，这些发育导致了这些成熟的神经电特性。这种综合方法强调了COs作为人脑发育和神经系统疾病的新兴模型系统的价值。