AUTHOR=Yaron Amit , Zhang Zhuo , Akita Dai , Shiramatsu Tomoyo Isoguchi , Chao Zenas C. , Takahashi Hirokazu TITLE=Dissociated neuronal cultures as model systems for self-organized prediction JOURNAL=Frontiers in Neural Circuits VOLUME=Volume 19 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/neural-circuits/articles/10.3389/fncir.2025.1568652 DOI=10.3389/fncir.2025.1568652 ISSN=1662-5110 ABSTRACT=Dissociated neuronal cultures provide a powerful, simplified model for investigating self-organized prediction and information processing in neural networks. This review synthesizes and critically examines research demonstrating their fundamental computational abilities, including predictive coding, adaptive learning, goal-directed behavior, and deviance detection. A unique contribution of this work is the integration of findings on network self-organization, such as the development of critical dynamics optimized for information processing, with emergent predictive capabilities, the mechanisms of learning and memory, and the relevance of the free energy principle within these systems. Building on this, we discuss how insights from these cultures inform the design of neuromorphic and reservoir computing architectures, aiming to enhance energy efficiency and adaptive functionality in artificial intelligence. Finally, this review outlines promising future directions, including advancements in three-dimensional cultures, multi-compartment models, and brain organoids, to deepen our understanding of hierarchical predictive processes in both biological and artificial systems, thereby paving the way for novel, biologically inspired computing solutions.