Alam El Din Dowlette-Mary, Moenkemoeller Leah, Loeffler Alon, Habibollahi Forough, Schenkman Jack, Mitra Amitav, van der Molen Tjitse, Ding Lixuan, Laird Jason, Schenke Maren, Johnson Erik C, Kagan Brett J, Hartung Thomas, Smirnova Lena
Center for Alternatives to Animal Testing (CAAT), Johns Hopkins University, Baltimore, MD, USA.
Department of Environmental Health and Engineering, Johns Hopkins University, Baltimore, MD, USA.
Commun Biol. 2025 Aug 16;8(1):1237. doi: 10.1038/s42003-025-08632-5.
Brain Microphysiological Systems, including neural organoids derived from human induced pluripotent stem cells, offer a unique lens to study the intricate workings of the human brain. This paper investigates the foundational elements of learning and memory in neural organoids by quantifying immediate early gene expression in response to chemical modulation, input-specific short- and long-term synaptic plasticity, neuronal network dynamics, connectivity, and criticality to demonstrate the utility of these organoids in basic science research. Neural organoids showed synapse formation, glutamatergic and GABAergic receptor expression, immediate early gene expression basally and evoked, functional connectivity, criticality, and synaptic plasticity in response to theta-burst stimulation. In addition, pharmacological interventions on GABAergic and glutamatergic receptors and input-specific theta-burst stimulation further shed light on the capacity of neural organoids to mirror synaptic modulation, specifically short- and long-term potentiation and depression, demonstrating their potential as tools for studying neurophysiological and neurological processes and informing therapeutic strategies for diseases.
脑微生理系统，包括源自人类诱导多能干细胞的神经类器官，为研究人类大脑的复杂运作提供了一个独特的视角。本文通过量化即刻早期基因表达以响应化学调节、输入特异性短期和长期突触可塑性、神经网络动力学、连通性和临界性，来研究神经类器官中学习和记忆的基础要素，以证明这些类器官在基础科学研究中的实用性。神经类器官显示出突触形成、谷氨酸能和γ-氨基丁酸能受体表达、基础和诱发的即刻早期基因表达、功能连通性、临界性以及对θ波爆发刺激的突触可塑性。此外，对γ-氨基丁酸能和谷氨酸能受体的药理学干预以及输入特异性θ波爆发刺激进一步揭示了神经类器官反映突触调节的能力，特别是短期和长期增强与抑制，证明了它们作为研究神经生理和神经学过程的工具以及为疾病治疗策略提供信息的潜力。
