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The neurobiological foundation of memory retrieval

Nature Neuroscience volume 22, pages 1576–1585 (2019)Cite this article

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Abstract

Memory retrieval involves the interaction between external sensory or internally generated cues and stored memory traces (or engrams) in a process termed ‘ecphory’. While ecphory has been examined in human cognitive neuroscience research, its neurobiological foundation is less understood. To the extent that ecphory involves ‘reawakening’ of engrams, leveraging recently developed technologies that can identify and manipulate engrams in rodents provides a fertile avenue for examining retrieval at the level of neuronal ensembles. Here we evaluate emerging neuroscientific research of this type, using cognitive theory as a guiding principle to organize and interpret initial findings. Our Review highlights the critical interaction between engrams and retrieval cues (environmental or artificial) for memory accessibility and retrieval success. These findings also highlight the intimate relationship between the mechanisms important in forming engrams and those important in their recovery, as captured in the cognitive notion of ‘encoding specificity’. Finally, we identify several questions that currently remain unanswered.

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Fig. 1: Tulving and Pearlstone’s experiment on retrieval failure1.
Fig. 2: Preventing and inducing ecphory by direct manipulation of fear memory engrams.
Fig. 3: Ecphory for an artificially generated engram.
Fig. 4: Silencing of the engram. Engrams exist in different states of accessibility.

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Acknowledgements

We thank A.Ramsaran and A.Park for drawing the figures, and we thank T. Ryan for comments on an earlier draft of this manuscript. This work was supported by Canadian Institutes of Health Research grants to P.W.F. (FDN-143227) and S.A.J. (FDN-388455) and a Natural Sciences and Engineering Research Council Discovery grant to S.K. (RGPIN-5770).

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Authors and Affiliations

  1. Program in Neurosciences & Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada

    Paul W. Frankland & Sheena A. Josselyn

  2. Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada

    Paul W. Frankland & Sheena A. Josselyn

  3. Department of Psychology, University of Toronto, Toronto, Ontario, Canada

    Paul W. Frankland & Sheena A. Josselyn

  4. Department of Physiology, University of Toronto, Toronto, Ontario, Canada

    Paul W. Frankland & Sheena A. Josselyn

  5. Child & Brain Development Program, Canadian Institute for Advanced Research, Toronto, Ontario, Canada

    Paul W. Frankland

  6. Brain, Mind & Consciousness Program, Canadian Institute for Advanced Research, Toronto, Ontario, Canada

    Sheena A. Josselyn

  7. Department of Psychology, University of Western Ontario, London, Ontario, Canada

    Stefan Köhler

  8. The Brain and Mind Institute, University of Western Ontario, London, Ontario, Canada

    Stefan Köhler

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  1. Paul W. Frankland
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Frankland, P.W., Josselyn, S.A. & Köhler, S. The neurobiological foundation of memory retrieval. Nat Neurosci 22, 1576–1585 (2019). https://doi.org/10.1038/s41593-019-0493-1

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