Neuro-X seminar: Prof Tomoya Duenki - Emergent Neural Dynamics in Scalable Brain Organoid Networks

Reconstructing physiologically relevant neuronal networks in vitro is essential for advancing our understanding of brain development, function, and disease. Human cerebral organoids provide a promising platform, but conventional systems remain limited in structural complexity, connectivity, and scalability for studying large-scale neural dynamics. To address these limitations, we engineered modular organoid networks, termed “connectoids,” in which multiple organoids are connected through guided axon bundles using microfluidic devices. Electrical recordings revealed that increasing network size from single organoids to multi-organoid connectoids resulted in progressively more complex neural dynamics, including prolonged activity periods, richer and more diverse bursting patterns, the emergence of functionally specialized network nodes, and network states approaching criticality. Pharmacological perturbations confirmed robust excitatory and inhibitory network responses, while optogenetic and electrical stimulation demonstrated controllable propagation and entrainment of activity across the network. Together, these scalable connectoid systems provide a platform for investigating emergent neural dynamics, structure–function relationships, and circuit organization across different levels of network complexity.