Windows of change: Revisiting temporal and molecular dynamics of memory reconsolidation and persistence

Retrieval can bring memories to a labile state, creating a window to modify its content during reconsolidation. Numerous studies have investigated this period to elucidate reconsolidation mechanisms, understand long-term memory persistence, and develop therapeutic strategies for memory-related psychiatric disorders. However, the temporal dynamics of post-retrieval memory processes have been largely overlooked, leading to mixed findings and hindering the development of targeted interventions. This review discusses retrieval-related cellular and molecular events and how they develop in series and parallel across time. Emerging evidence suggests that some mechanisms triggered after fear memory retrieval can influence either reconsolidation or persistence in different time windows. The temporal boundaries of these post-retrieval processes are still unclear. Further research integrating behavioral and molecular approaches to a deeper understanding of reconsolidation and persistence temporal dynamics is essential to address current debates, including which system/pathway offers the most effective therapeutic window of opportunity.