The dorsal hippocampus mediates synaptic destabilization and memory lability in the amygdala in the absence of contextual novelty

The recall of a previously formed fear memory triggers a process through which synapses in the amygdala become destabilized. This labile state at retrieval may be critical for the plasticity required to modify, update, or disrupt long-term memories. One component of this process involves the rapid internalization of calcium impermeable AMPA receptors (CI-AMPAR). While some recent work has focused on the details of modifying amygdala synapses, much less is known about the environmental factors that control memory updating and the important circuit level processes. Synchrony between the hippocampus and amygdala increases during memory retrieval and stable memories can sometimes be made labile with hippocampal manipulations. Recent work shows that memory lability at retrieval is influenced by the novelty of the retrieval environment, and detection of this novelty likely relies on the dorsal hippocampus (DH). Our goal was to determine how local activity in the DH contributes to memory lability and synaptic destabilization in the amygdala during retrieval when contextual novelty is introduced. We found that contextual novelty during retrieval is necessary for alterations in amygdala activity and CI-AMPAR internalization. In the absence of novelty, suppression of local activity in the DH prior to learning allowed for retrieval-dependent CI-AMPAR internalization in the amygdala. We next tested whether the changes in AMPAR internalization were accompanied by differences in memory lability. We found that a memory was made labile when activity within the DH was disrupted in the absence of contextual novelty. These results suggest that the DH is important for encoding contextual information during learning that regulates retrieval-dependent memory modification in the amygdala.