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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.2025.07.011 | DOI Listing |
Front Cell Neurosci
July 2025
Institute for Advanced Brain Studies, Lomonosov Moscow State University, Moscow, Russia.
In a healthy brain, the reactivation of memories under conditions of novelty leads to their labilization and subsequent reconsolidation. However, if plasticity of the nervous system is reduced reconsolidation mechanisms may be disrupted, leading to weakening and loss of existing memory. We hypothesize that such self-degradation of old memory due to its reactivation in the compromised brain may lead to progressive memory loss in Alzheimer's disease.
View Article and Find Full Text PDFTrends Neurosci
August 2025
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.
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.
View Article and Find Full Text PDFNat Hum Behav
August 2025
Department of Neuropsychology, Institute of Cognitive Neuroscience, Faculty of Psychology, Ruhr University Bochum, Bochum, Germany.
Extinction learning-the suppression of a previously acquired fear response-is critical for adaptive behaviour and core for understanding the aetiology and treatment of anxiety disorders. Electrophysiological studies in rodents have revealed critical roles of theta (4-12 Hz) oscillations in amygdala and hippocampus during both fear learning and extinction, and engram research has shown that extinction relies on the formation of novel, highly context-dependent memory traces that suppress the initial fear memories. Whether similar processes occur in humans and how they relate to previously described neural mechanisms of episodic memory formation and retrieval remains unknown.
View Article and Find Full Text PDFPLoS Comput Biol
July 2025
Department of Mathematical Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea.
Engrams corresponding to distinct memories compete for retrieval in the CA3 region of the hippocampus, yet the detailed mechanisms underlying their formation remain elusive. Recent findings indicate that hippocampal inhibitory neurons display feature-selective firing patterns and diverse forms of synaptic plasticity, suggesting a crucial role in engram formation. Conventional CA3 attractor network models typically employ global inhibition, where inhibitory neurons uniformly suppress the activity of excitatory neurons.
View Article and Find Full Text PDFFront Pharmacol
July 2024
Institute for Advanced Brain Studies, Lomonosov Moscow State University, Moscow, Russia.
Reactivation of already consolidated memory can initiate its destabilization, making the memory trace labile. Normally, this destabilization is followed by reconsolidation of the memory trace, enriched by newly acquired experience. Disrupting the reconsolidation process, for example, by inhibiting protein synthesis, impairs subsequent memory retrieval, leading to reminder-related amnesia.
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