The cost of remembering: engram competition as a flexible mechanism of forgetting.

Trends Neurosci

School of Biochemistry and Immunology, Trinity College of Dublin, Dublin, Ireland; Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland; Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Melbourne, Victoria, Australia.

Published: August 2025


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Article Abstract

The retention and use of long-term memories is crucial for adaptive behavior. While stable memories help organisms anticipate outcomes, they may become maladaptive if not updated to reflect new conditions as the environment changes. Accumulating evidence suggests that forgetting reflects altered activation of engram cells, with memories persisting in a latent state rather than being erased. One explanation for the forgetting of particular memories is active competition between memory engrams for expression in the brain. Behavioral studies reveal that various forms of forgetting stem from this competition. Here we synthesize behavioral research through the lens of engram competition, focusing on its biological substrates and driving factors. We propose a framework to better understand diverse forms of natural forgetting as well as associated pathological conditions.

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http://dx.doi.org/10.1016/j.tins.2025.07.011DOI Listing

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