Neurons differentiated from induced pluripotent stem cells (iPSCs) typically show regular spiking and synaptic activity but lack more complex network activity critical for brain development, such as periodic depolarizations including simultaneous involvement of glutamatergic and GABAergic neurotransmission. We generated human iPSC-derived neurons exhibiting spontaneous oscillatory activity after cultivation of up to 6 months, which resembles early oscillations observed in rodent neurons. This behavior was found in neurons generated using a more “native” embryoid body protocol, in contrast to a “fast” protocol based on NGN2 overexpression. A comparison with published data indicates that EB-derived neurons reach the maturity of neurons of the third trimester and NGN2-derived neurons of the second trimester of human gestation. Co-culturing NGN2-derived neurons with astrocytes only led to a partial compensation and did not reliably induce complex network activity. Our data will help selection of the appropriate iPSC differentiation assay to address specific questions related to neurodevelopmental disorders.

从诱导多能干细胞（iPSC）分化出来的神经元通常表现出规律的加标和突触活动，但缺乏对大脑发育至关重要的更复杂的网络活动，例如周期性去极化，包括同时参与谷氨酸能和GABA能神经传递。在培养长达6个月后，我们生成了人类iPSC衍生的神经元，其表现出自发的振荡活性，这与在啮齿动物神经元中观察到的早期振荡相似。与使用基于NGN2过表达的“快速”协议相比，使用更“天然”的胚状体协议生成的神经元中发现了这种行为。与已发表数据的比较表明，EB衍生的神经元达到了妊娠中期和晚期妊娠的NGN2衍生神经元。将NGN2衍生的神经元与星形胶质细胞共培养只会导致部分补偿，并且不能可靠地诱导复杂的网络活动。我们的数据将有助于选择合适的iPSC分化检测方法，以解决与神经发育障碍有关的特定问题。