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

• Published in: Nature communications Vol. 15; no. 1; p. 2945
• Main Authors: Osaki, Tatsuya, Duenki, Tomoya, Chow, Siu Yu A., Ikegami, Yasuhiro, Beaubois, Romain, Levi, Timothée, Nakagawa-Tamagawa, Nao, Hirano, Yoji, Ikeuchi, Yoshiho
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.04.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/107; 13/62; 14; 14/19; 14/63; 38; 631/378/2571/2577; 631/378/2591/2594; 631/378/87; 631/61/2035; 64; 9/10; 9/74; Axons; Axons - physiology; Brain; Circuits; Connecting; Humanities and Social Sciences; Humans; Investigations; multidisciplinary; Neural networks; Neural plasticity; Neurons; Neurons - physiology; Neurosciences; Organoids; Organoids - physiology; Plastic properties; Plasticity; Regional development; Science; Science (multidisciplinary); Stimulation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-46787-7

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. Connecting cerebral organoids with an axon bundle models inter-regional projections and enhances neural activity. Optogenetic stimulation induces short-term plasticity, offering insights into macroscopic circuit development and functionality.