RECONSOLIDATION-DEPENDENT UPDATING OF SOCIAL MEMORY IN VENTRAL HIPPOCAMPAL CA1

Social memory (SM), the ability to recognize familiar conspecifics, is essential for adaptive social behavior. However, whether SM can be updated, and the underlying neural mechanisms remain unclear. Here, we tested the hypothesis that SM updating relies on reconsolidation mechanisms in the ventral CA1 (vCA1) of the hippocampus. Male C57BL/6 mice with vCA1 cannulae were assessed in two social recognition tasks. Task 1 examined SM updating after a context change designed to induce prediction error, and Task 2 probed SM modification following disruption of expected social cues. In both tasks, mice received intra-vCA1 anisomycin (ANI) or saline immediately after the prediction-error session, and SM was reassessed 24 h later. ANI selectively disrupted SM, whereas saline-treated mice retained memory, indicating that SM updating is protein synthesis-dependent. In Task 1, destabilization required both novelty and memory reactivation, as ANI had no effect without a context change, after prolonged habituation, or in absence of recall. In Task 2, omission of the expected social stimulus triggered SM destabilization, and ANI blocked reconsolidation process, preventing SM updating and altering the duration of social interactions bouts. Notably, SM lability was restricted to a limited temporal window, as ANI administered 6 hours post–prediction error had no effect. Collectively, these results reveal that SM lability is prediction-error dependent, recall-contingent, and time-limited, and that vCA1 protein synthesis is essential for reconsolidation-mediated updating of SM These findings advance our understanding of the neural mechanisms underlying flexible social behavior and may guide clinical approaches for the treatment of traumatic memories.