Custom scripts for "Advanced Complexity and Short-Term 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.作为一种用于研究长程神经元环路的类器官（organoid）模型，本研究针对两组通过轴突相互连接的独立大脑类器官（cerebral organoids）的神经元活动展开了探究。令人瞩目的是，与常规培养或直接融合的两组大脑类器官相比，该连接类器官展现出显著更强且更复杂的振荡活动。轴突连接同时还可促进类器官中特定细胞群的发育成熟。作为宏观神经元网络，该连接类器官能够响应周期性外部刺激，并展现出复杂的可塑性模式。上述研究结果表明，轴突投射并非仅能传递信号，更可提升大脑类器官的功能复杂度与成熟度。本研究佐证了「大脑内部的区域间连接是催生功能复杂度的核心结构」这一观点，由此为体外探究宏观神经元环路的发育与功能提供了全新的研究路径。