Adaptive Expression of Engrams by Retroactive Interference

Long-term memories are stored as configurations of neuronal ensembles, termed engrams. Although inves-tigation 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 labeling, we show that although retro-active interference results in decreased engram cell reactivation during recall trials, optogenetic stimulation of the labeled engram cells is sufficient to induce memory retrieval. Forgotten engrams may 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 inter-ference modules engram expression in a manner that is both reversible and updatable. Inference may consti-tute a form of adaptive forgetting where, in everyday life, new perceptual and environmental inputs modulate the natural forgetting process.