Developmental changes in brain-wide fear memory networks

Memory retrieval involves coordinated activity across multiple brain regions. Yet how the organization of memory networks evolves throughout development remains poorly understood. In this study, we compared whole-brain functional networks that are active during contextual fear memory recall in infant, juvenile, and adult mice. Our analyses revealed that long-term memory networks change significantly across postnatal development. Infant fear memory networks are dense and heterogeneous, whereas adult networks are sparse and have a small-world topology. While hippocampal subregions were highly connected nodes at all ages, the cortex gained many functional connections across development. Different functional connections matured at different rates, but their developmental timing fell into three major categories: stepwise change between two ages, linear change across all ages, or inverted-U, with elevated functional connectivity in juveniles. Our work highlights how a subset of brain regions likely maintain important roles in fear memory encoding, but the functional connectivity of fear memory networks undergoes significant reorganization across development. Together, these results provide a blueprint for studying how correlated cellular activity in key areas distinctly regulates memory storage and retrieval across development.