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.作为一种用于长距离神经元环路的类器官模型，本研究探究了由轴突（axon）实现相互连接的两个独立大脑类器官（cerebral organoid）的神经元活动。值得注意的是，相较于常规培养的双脑类器官或直接融合的双脑类器官，相互连接的类器官所产生的振荡活动强度显著更高、复杂度也更为突出。轴突连接还可促进类器官中特定细胞群的发育成熟。该相互连接的类器官能够响应周期性外部刺激，并作为宏观神经元网络展现出复杂的可塑性模式。上述研究结果表明，轴突投射不仅能够简单传递信号，更能提升大脑类器官的功能复杂度与发育成熟度。本研究佐证了“脑内区域间连接是产生功能复杂度的核心结构”这一观点，并为体外探究宏观神经元环路的发育与功能开辟了新的途径。