GABAergic interneuron diversity and organization are crucial for the generation of human-specific functional neural networks in cerebral organoids

Abstract

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This mini review investigates the importance of GABAergic interneurons for the network function of human-induced pluripotent stem cells (hiPSC)-derived brain organoids. The presented evidence suggests that the abundance, diversity and three-dimensional cortical organization of GABAergic interneurons are the primary elements responsible for the creation of synchronous neuronal firing patterns. Without intricate inhibition, coupled oscillatory patterns cannot reach a sufficient complexity to transfer spatiotemporal information constituting physiological network function. Furthermore, human-specific brain network function seems to be mediated by a more complex and interconnected inhibitory structure that remains developmentally flexible for a longer period when compared to rodents. This suggests that several characteristics of human brain networks cannot be captured by rodent models, emphasizing the need for model systems like organoids that adequately mimic physiological human brain function in vitro.

Keywords

• human-specific inhibition
• GABAergic interneurons
• E-I balance
• phase-amplitude-coupling
• functional neural networks
• 2D/3D neuronal cell culture