Review Article | Published:

The role of engram cells in the systems consolidation of memory

Nature Reviews Neurosciencevolume 19pages485498 (2018) | Download Citation


What happens to memories as days, weeks and years go by has long been a fundamental question in neuroscience and psychology. For decades, researchers have attempted to identify the brain regions in which memory is formed and to follow its changes across time. The theory of systems consolidation of memory (SCM) suggests that changes in circuitry and brain networks are required for the maintenance of a memory with time. Various mechanisms by which such changes may take place have been hypothesized. Recently, several studies have provided insight into the brain networks driving SCM through the characterization of memory engram cells, their biochemical and physiological changes and the circuits in which they operate. In this Review, we place these findings in the context of the field and describe how they have led to a revamped understanding of SCM in the brain.

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  1. RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Departments of Biology and Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA

    • Susumu Tonegawa
    •  & Mark D. Morrissey
  2. Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA

    • Susumu Tonegawa
  3. Department of Psychiatry and Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA

    • Takashi Kitamura


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M.D.M. and T.K. researched data for the article. S.T., M.D.M. and T.K. made substantial contributions to discussions of the content, wrote the article and reviewed and/or edited the manuscript before submission.

Competing interests

The authors declare no competing interests.

Corresponding authors

Correspondence to Susumu Tonegawa or Mark D. Morrissey or Takashi Kitamura.


Episodic memory

The recollection of events with a specific spatial and temporal context, such as personal experiences. Often referred to as autobiographical memory.


The use of genetically encoded light-activated proteins (for example, ion channels) to control functional parameters (for example, the membrane potential) of targeted neuronal populations.

Trace eyeblink conditioning

A form of classical conditioning extensively used to study neural structures and mechanisms that underlie learning and memory. It is based on a relatively simple procedure that often consists of pairing an auditory (or visual) stimulus with an eyeblink-eliciting unconditioned stimulus (such as a mild puff of air to the cornea or a mild shock), with the two stimuli being separated by a stimulus-free trace interval.

Immediate early gene

A gene that encodes a transcription factor that is induced within minutes of raised neuronal activity without requiring a protein signal. Immediate early gene activation is, therefore, used as an indirect marker of neuronal activation.

Contextual fear conditioning

(CFC). A behavioural test in which an aversive stimulus is given to an animal in a conditioning chamber, such that the fear response can subsequently be elicited in the conditioning chamber in the absence of the aversive stimulus.

Morris water maze

A hippocampus-dependent spatial learning and memory task in which a rodent learns the position of an escape platform placed beneath the surface of a pool of opaque water using a set of distal extra-maze visual cues.

Trace fear conditioning

An associative memory task in which a stimulus (the conditioned stimulus, such as a tone) predicts an aversive stimulus (the unconditioned stimulus, such as a footshock), with the two stimuli being separated by a stimulus-free trace interval. Subsequent presentation of the conditioned stimulus alone in a neutral context can elicit a fear response.

Paired-associate memory

A memory task in which arbitrary paired associations are learned and recalled, for example, certain locations in a space may be paired with a particular object or flavour of food reward.

Social transmission of food preference paradigm

A memory paradigm in rodents that takes advantage of the animals’ natural food neophobia. If a naive subject rat interacts with a demonstrator rat that has recently sampled a particular novel food substance, the naive animal acquires a preference for that food that can persist for many days.

Sharp-wave ripples

Brief (approximately 100 ms) episodes of high-frequency (>100 Hz) population activity.

Semantic memories

Recollections of factual information that are independent of the specific episodes in which that information was acquired.

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