PT  - JOURNAL ARTICLE
AU  - Kyle Puhger
AU  - Brian J. Wiltgen
TI  - The hippocampus contributes to retroactive stimulus associations in trace fear conditioning
AID  - 10.1101/2022.10.17.512614
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.10.17.512614
4099  - http://biorxiv.org/content/early/2022/10/21/2022.10.17.512614.short
4100  - http://biorxiv.org/content/early/2022/10/21/2022.10.17.512614.full
AB  - Animals with damage to the dorsal hippocampus can acquire fear to an auditory stimulus (CS) that co-terminates with a footshock (US) but those with amygdala damage cannot. However, if the US occurs after a temporal gap (trace conditioning) a functioning hippocampus is required to associate them. It is often assumed this is the case because the dorsal hippocampus maintains a memory of the CS until the US is presented. However, neurophysiological recordings have not observed persistent activity after the tone CS in the hippocampus similar to that observed in the prefrontal cortex during working memory tasks. Therefore, in the current study, we tested a novel hypothesis about the contribution of the hippocampus to trace fear conditioning (TFC). We propose that CS and US representations may become linked in the hippocampus after a learning trial ends. To test the idea, we first used fiber photometry to examine GCaMP activity in dorsal CA1 during TFC. We found a large and sustained increase in activity after the footshock that lasted for approximately 40-sec. To determine if this increase was important for TFC, we inactivated dorsal CA1 during this period using the inhibitory opsin ArchT. We found that memory was impaired when dorsal CA1 was silenced for 40-sec immediately after the footshock had terminated. The same manipulation had no effect when it occurred during the intertrial interval. Finally, we found that post-shock activity in dorsal CA1 was required early, but not late in training. These data suggest that the dorsal hippocampus may link events that are separated in time by reactivating memories of them after they occur.Competing Interest StatementThe authors have declared no competing interest.