Forgetting as a form of adaptive engram cell plasticity

• Published in: Nature reviews. Neuroscience Vol. 23; no. 3; pp. 173 - 186
• Main Authors: Ryan, Tomás J., Frankland, Paul W.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-03-2022; Nature Publishing Group
• Subjects: 631/378/1595/2639; 631/378/3920; Amnesia; Animal Genetics and Genomics; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Environmental conditions; Experiments; Memory; Neural plasticity; Neurobiology; Neurosciences; Perspective; Protein synthesis; Proteins; Recall
• ISSN: 1471-003X; 1471-0048; 1469-3178
• DOI: 10.1038/s41583-021-00548-3

One leading hypothesis suggests that memories are stored in ensembles of neurons (or ‘engram cells’) and that successful recall involves reactivation of these ensembles. A logical extension of this idea is that forgetting occurs when engram cells cannot be reactivated. Forms of ‘natural forgetting’ vary considerably in terms of their underlying mechanisms, time course and reversibility. However, we suggest that all forms of forgetting involve circuit remodelling that switches engram cells from an accessible state (where they can be reactivated by natural recall cues) to an inaccessible state (where they cannot). In many cases, forgetting rates are modulated by environmental conditions and we therefore propose that forgetting is a form of neuroplasticity that alters engram cell accessibility in a manner that is sensitive to mismatches between expectations and the environment. Moreover, we hypothesize that disease states associated with forgetting may hijack natural forgetting mechanisms, resulting in reduced engram cell accessibility and memory loss.
Deciphering the mechanisms that cause encoded memories to be forgotten may help us to understand both adaptive forgetting and pathological memory loss. In this Perspective, Tomás Ryan and Paul Frankland propose that forgetting involves neuroplasticity that alters engram cells accessibility and is governed by changes in environmental predictability.