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Molecular mechanisms of memory reconsolidation

Nature Reviews Neuroscience volume 8, pages 262–275 (2007)Cite this article

Key Points

  • Reconsolidation has been conceptualized as a post-retrieval process that stabilizes memory made labile by retrieval. This theory remains controversial, and one major question is whether post-retrieval disruptions of memory are permanent, suggesting erasure and therefore a storage mechanism, or transient, suggesting that the memory trace remains intact.

  • Molecular mechanisms of memory reconsolidation have been shown to have substantial but incomplete overlap with those of initial consolidation, supporting the assertion that reconsolidation may be a storage process.

  • Studies utilizing inhibition and activation of intracellular signalling proteins have shown that transcription factors including CREB, C/EBPβ and ZIF268, as well as upstream protein kinases including PKA and ERK, are required for memory reconsolidation,

  • Additional molecular cascades, including transcription factor ELK1, immediate early genes c-Fos and Sgk3, and the protein kinase ERK are activated after memory reactivation, indicating a role for these pathways in reconsolidation.

  • Disruption of memory reconsolidation may be useful for intervention in psychiatric disorders involving abnormally strong or intrusive memories, such as post-traumatic stress disorder.

  • Abnormal reconsolidation processes might contribute to the development of psychiatric disorders such as drug addiction, where long-term adaptation of cell signalling pathways can contribute to ongoing enhancements of reconsolidation, thereby strengthening the maladaptive memory and leading to long-lasting, relapsing behavioural changes.

  • In order to move forward and answer some of the ongoing controversies, research in reconsolidation needs to diverge from purely behavioural models to demonstrate electrophysiological and structural correlates of post-retrieval manipulations of memory.

Abstract

Memory reconsolidation has been argued to be a distinct process that serves to maintain, strengthen or modify memories. Specifically, the retrieval of a previously consolidated memory has been hypothesized to induce an additional activity-dependent labile period during which the memory can be modified. Understanding the molecular mechanisms of reconsolidation could provide crucial insights into the dynamic aspects of normal mnemonic function and psychiatric disorders that are characterized by exceptionally strong and salient emotional memories.

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Figure 1: Experimental design for reconsolidation experiments.
Figure 2: Key molecular mechanisms of memory reconsolidation.
Figure 3: Bidirectional plasticity after memory retrieval modulated by PKA.

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Acknowledgements

We would like to thank J. J. Quinn and G. E. Schafe for helpful comments and discussion on this manuscript and topic. We would also like to sincerely thank the reviewers for their insight and helpful criticisms and comments on this review. This work was supported by United States Public Health Service grants to J.R.T. and by the Abraham Ribicoff Research Facilities of the Connecticut Mental Health Center, State of Connecticut, Department of Mental Health and Addiction Services.

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  1. Department of Psychiatry, Division of Molecular Psychiatry, Center for Genes and Behavior, Yale University School of Medicine, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park Street, New Haven, 06508, Connecticut, USA

    Natalie C. Tronson & Jane R. Taylor

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Correspondence to Jane R. Taylor.

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Glossary

Consolidation

The process by which new memories are stored after a novel learning experience.

Retrieval

Return of a previously established memory into consciousness, resulting in lability of the memory.

Memory trace

Refers to the memory, stored as a result of the modification of synapses.

Lability

Instability of a previously consolidated memory, as identified by its susceptibility to manipulation.

Reconsolidation

The process by which previously consolidated memories are stabilized after retrieval.

Plasticity

Physical changes in neuronal connections or morphology as a result of external stimulation that results in long-lasting functional changes in excitability in a system of neurons. These physical changes at synapses underlie experience-dependent long-lasting changes in behaviour and memory.

Pavlovian conditioning

Procedure in which a stimulus (conditioned stimulus) — such as a tone — that elicits no response on its own, is paired with a biologically relevant stimulus (unconditioned stimulus) — such as footshock — during training. After consolidation, the conditioned stimulus elicits a conditioned response.

Reactivation

Cued retrieval of a memory under experimental conditions. In experiments on reconsolidation, reactivations are usually presentations of the previously conditioned stimulus or context. The length of the reactivation can be modified by changing the length of exposure to the conditioned stimulus or context.

Extinction

Refers either to the learning process by which a cue (or action) previously associated with a reinforcer becomes newly associated with no outcome, leading to a decrease in the previously established conditioned response or to the procedure by which a cue or action previously paired with a reinforcer is now paired with no reinforcer.

Spontaneous recovery

Retrieval of a previously extinguished memory, usually after a long period of time (weeks) after extinction, in the absence of experimental manipulation, retraining or changes in context.

Reinstatement

Retrieval of an extinguished memory after unpaired exposure to the unconditioned stimulus.

Inactive avoidance

(IA). A fear conditioning procedure in which an animal has to learn to inhibit a naturally occurring response (for example moving from a light area to a dark area) in order to avoid an aversive event (such as footshock).

Conditioned place preference

(CPP). Behavioural test in which an unconditioned stimulus is paired with one distinctive context, and a neutral event is paired with a different context. Preference is determined by allowing the animal to move between the two contexts, and measuring the amount of time spent in each context.

Double dissociation

Situation in which one experimental manipulation affects process A but not process B, and a second manipulation affects process B but not process A. Meeting both of these criteria for a double dissociation is considered strong evidence for two separable processes.

Second-order conditioning

Procedure in which a previously conditioned stimulus is used as the reinforcer for conditioning a second stimulus.

Long-term potentiation

(LTP). The prolonged strengthening of synaptic communication, which is induced by patterned input and is thought to be involved in learning and memory formation.

Long-term depression

(LTD) A persistent reduction of synaptic transmission in response to weak, poorly-correlated input.

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Tronson, N., Taylor, J. Molecular mechanisms of memory reconsolidation. Nat Rev Neurosci 8, 262–275 (2007). https://doi.org/10.1038/nrn2090

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