TIME IN ASSOCIATIVE FEAR MEMORIES: THE ROLE OF HIPPOCAMPUS

Time plays a crucial role in memory; however, the relationship between event duration, temporal sequences, and memory acquisition remains unclear. We have recently uncovered a key temporal rule that determines whether fearful events become linked to neutral ones and are consolidated together. Specifically, we found that the association or dissociation of events is influenced by the time elapsed between them. Fearful and neutral events are associated when the interval between them is shorter than 30 minutes. Interestingly, at a 30-minute interval, we observed that in approximately half of the trained animals the responses to both fearful and neutral cues were very low, suggesting that the neutral event interferes with the consolidation of the fearful event. These findings indicate individual variability in how fearful events are associated with neutral events. Notably, modulation of thalamic input to the lateral amygdala alters this temporal rule. Here, we investigated whether the hippocampus is involved in defining the time window during which events can be associated. To this end, we employed a training protocol that increases hippocampal involvement in cue–fear conditioning. We found that fear-memory association under an ambiguous training regime follows the same temporal rules as those observed under a predictive training regime. Importantly, interfering with hippocampal activity disrupted fear-memory association when it was acquired under the ambiguous training regime. Together, these results suggest that time is a critical parameter determining hippocampal contribution to fear-memory consolidation.
Work funded by National Funds through FCT—Fundação Ciência e Tecnologia, I.P., project 2022.09002.PTDC