01980nas a2200301   4500000000100000000000100001008004100002260001500043653002600058653002800084653002500112653002300137100001800160700001800178700001900196700002100215700002000236700001900256700002600275700001600301700002000317245010900337856005500446300000900501490000700510520114700517022001401664       2024                            d  c2024-04-1010aCellular neuroscience10aShort-term potentiation10aSynaptic development10aTissue engineering1 aTatsuya Osaki1 aTomoya Duenki1 aSiu Yu A. Chow1 aYasuhiro Ikegami1 aRomain Beaubois1 aTimothée Levi1 aNao Nakagawa-Tamagawa1 aYoji Hirano1 aYoshiho Ikeuchi00aComplex activity and short-term plasticity of human cerebral organoids reciprocally connected with axons  uhttps://www.nature.com/articles/s41467-024-46787-7  a29450 v153 aAn 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.  a2041-1723