Custom scripts for "Advanced Complexity and Plasticity of Neural Activity in Reciprocally Connected Human Cerebral Organoids"

As an organoid model for a long-range neuronal circuitry, we investigated neuronal activity of two separate cerebral organoids reciprocally connected by axons. Strikingly, the connected organoids produced significantly more intense and complex oscillatory activity than conventional or directly fused two cerebral organoids. The axonal connections also promoted developmental maturation in a distinct cellular population of the organoids. The connected organoids could follow periodic external stimuli and exhibit complex patterns of plasticity as a macroscopic neuronal network. These results demonstrated that axonal projections not just simply transmit signals, but rather enhance complexity and functional maturity of the cerebral organoids. This study supports the idea that the inter-regional connections within brains are the key structures for generating functional complexity. It thus paves a way for investigating development and functions of macroscopic neuronal circuits in vitro.