Adaptive Expression of Engrams by Retroactive Interference

SUMMARY Long-term memories are stored as stable configurations of neuronal ensembles, termed engrams. While investigation of engram cell properties and functionality in memory recall has been extensive, less is known about how engram cells are affected by forgetting. We describe a form of interference-based forgetting using an object memory behavioral paradigm. By using activity-dependent cell labelling, we show that although retroactive interference results in decreased engram cell reactivation during recall trials, optogenetic stimulation of the labelled engram cells is sufficient to induce memory retrieval. Forgotten engrams may also be reinstated via the presentation of similar or related environmental information. Furthermore, we demonstrate that engram activity is necessary for interference to occur. Taken together, these findings indicate that retroactive interference modulates engram expression in a manner that is both reversible and updatable. Retroactive inference may constitute a form of adaptive forgetting, where in everyday life new perceptual and environmental inputs modulate the natural forgetting process.