Complex activity and short-term plasticity of human cerebral organoids reciprocally connected with axons

Tatsuya Osaki, Tomoya Duenki, Siu Yu A. Chow, Yasuhiro Ikegami, Romain Beaubois, Timothée Levi, Nao Nakagawa-Tamagawa, Yoji Hirano and Yoshiho Ikeuchi ()
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Tatsuya Osaki: The University of Tokyo
Tomoya Duenki: The University of Tokyo
Siu Yu A. Chow: The University of Tokyo
Yasuhiro Ikegami: The University of Tokyo
Romain Beaubois: The University of Tokyo
Timothée Levi: The University of Tokyo
Nao Nakagawa-Tamagawa: The University of Tokyo
Yoji Hirano: The University of Tokyo
Yoshiho Ikeuchi: The University of Tokyo

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract An inter-regional cortical tract is one of the most fundamental architectural motifs that integrates neural circuits to orchestrate and generate complex functions of the human brain. To understand the mechanistic significance of inter-regional projections on development of neural circuits, we investigated an in vitro neural tissue model for inter-regional connections, in which two cerebral organoids are connected with a bundle of reciprocally extended axons. The connected organoids produced more complex and intense oscillatory activity than conventional or directly fused cerebral organoids, suggesting the inter-organoid axonal connections enhance and support the complex network activity. In addition, optogenetic stimulation of the inter-organoid axon bundles could entrain the activity of the organoids and induce robust short-term plasticity of the macroscopic circuit. These results demonstrated that the projection axons could serve as a structural hub that boosts functionality of the organoid-circuits. This model could contribute to further investigation on development and functions of macroscopic neuronal circuits in vitro.

Date: 2024
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DOI: 10.1038/s41467-024-46787-7

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