Adaptive expression of engrams by retroactive interference

• Published in: Cell reports (Cambridge) Vol. 42; no. 8; p. 112999
• Main Authors: Autore, Livia, O’Leary, James D., Ortega-de San Luis, Clara, Ryan, Tomás J.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 29-08-2023; Elsevier
• Subjects: c-Fos; consolidation; CP: Neuroscience; dentate gyrus; engram; false memory; forgetting; interference; memory; object/context memory; forgetting; dentate gyrus; memory; false memory; CP: Neuroscience; engram; c-Fos; interference; object/context memory; consolidation
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112999

Long-term memories are stored as configurations of neuronal ensembles, termed engrams. Although 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 labeling, we show that although retroactive 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 interference modules engram expression in a manner that is both reversible and updatable. Inference may constitute a form of adaptive forgetting where, in everyday life, new perceptual and environmental inputs modulate the natural forgetting process.
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•Retroactive interference causes forgetting by the competition of two memory engrams•Forgotten engrams can be expressed or updated by reexposure to training cues•Artificial reactivation of engram cells rescues interference-induced forgetting•Interference is an active process that requires the activation of the suppressed engram
Autore et al. advance our understanding of the role of memory engram cells in forgetting. This study shows that forgetting is an active process that modulates memory to be both reversible and updatable. Interference may cause adaptive forgetting, where newly formed engrams compete to modulate memory in everyday life.