Dentate gyrus circuits for encoding, retrieval and discrimination of episodic memories


The dentate gyrus (DG) has a key role in hippocampal memory formation. Intriguingly, DG lesions impair many, but not all, hippocampus-dependent mnemonic functions, indicating that the rest of the hippocampus (CA1–CA3) can operate autonomously under certain conditions. An extensive body of theoretical work has proposed how the architectural elements and various cell types of the DG may underlie its function in cognition. Recent studies recorded and manipulated the activity of different neuron types in the DG during memory tasks and have provided exciting new insights into the mechanisms of DG computational processes, particularly for the encoding, retrieval and discrimination of similar memories. Here, we review these DG-dependent mnemonic functions in light of the new findings and explore mechanistic links between the cellular and network properties of, and the computations performed by, the DG.

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Fig. 1: Anatomical organization of the hippocampus.
Fig. 2: Spatial, contextual and temporal firing characteristics of identified dentate gyrus neurons.
Fig. 3: Dentate gyrus functions in memory encoding and recall.
Fig. 4: Dentate gyrus function in discriminatory contextual fear conditioning.


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The authors’ work was supported by the Deutsche Forschungsgemeinschaft (FOR2143-2 and BA-1582/12-1, M.B.; HA 8939/1-1, T.H.), the European Research Council Advanced Grant (ERC-AdG 787450, M.B.), EMBO (European Molecular Biology Organization) (ALTF 6-2019, T.H.) and the Excellence Initiative of the German Research Foundation (GSC-4, Spemann Graduate School, T.H.; Brain-Links Brain-Tools, M.B.). The authors thank U. Häussler for providing the images of the human and mouse hippocampal slices, and they apologize for the fact that, owing to space limits, not all relevant papers could be cited.

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Correspondence to Thomas Hainmueller or Marlene Bartos.

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Semantic memories

Declarative memories that comprise general knowledge (for example, facts and concepts) about the world that is not bound to a distinct personal experience.

Episodic memories

Declarative memories that depict unique, personal experiences made in a distinct spatial and temporal context.


An experience-driven change to the brain that is stored and reactivated during memory recall. This may be a distinct neuronal ensemble, a sequential co-activation pattern of several neurons or a set of synaptic weights in a neuronal network.

Declarative memory

A memory of facts and events that can be consciously recollected and reported to others.

Trisynaptic loop

A canonical set of forward synaptic connections from the entorhinal cortex to the dentate gyrus via the perforant path, further to the CA3 via the mossy fibres and from there to the CA1 via the Schaffer collaterals.

Pattern separation

A network computation that generates more dissimilar output patterns in response to similar input patterns. Pattern separation is hypothesized to support the cognitive discrimination of similar representations in the brain.

Pattern completion

A computation in which slightly different input patterns activate a common, stored output pattern. This could promote retrieval of a complete stored memory from inputs representing partial cues or support generalization between similar memory contents.

Place field

The spatial location in which a hippocampal neuron, called a ‘place cell’, fires action potentials.


The process of changing place-field locations or the firing rate of neurons in a place field in response to contextual factors, such as environmental changes or altered behavioural demands.

Immediate early genes

(IEGs). Genes that usually encode transcription factors (such as FOS or ARC) that are induced within minutes after strong neuronal activation. High expression of IEGs in a neuron is commonly used as a read-out for recently elevated activity or synaptic plasticity.

NMDA receptor

(NMDAR). An ionotropic glutamate receptor that is highly prevalent at excitatory synapses in the central nervous system. The NMDAR is activated by coincident presynaptic glutamate release and postsynaptic neuronal depolarization, and is critical for many forms of synaptic plasticity.

Dentate spikes

Brief (20–80 ms), large-amplitude (1–3 mV), local-field potential activity patterns characteristic of the dentate gyrus, elicited by synchronous activation of a larger group of granule cells and other dentate neurons.

Sharp waves–ripples

(SWRs). Brief (40–150 ms), large-amplitude deflections of the local-field potential associated with synchronous high-frequency (110–200 Hz) network oscillations that originate in the CA3 and propagate into many other brain areas. SWRs occur during immobility and sleep, and play an important role in memory consolidation and other cognitive processes.

Contextual fear conditioning

(CFC). A behavioural paradigm in which an aversive stimulus (for example, a foot shock) is given in a defined experimental chamber. Fear memories are assessed by the amount of fear-related behaviour (for example, freezing) that an animal shows after re-exposure to the same chamber.

Attractor dynamics

The tendency of a process or neuronal network to fall into a continuous or discrete set of stable states (attractors) that are relatively resistant to external perturbations. Activity states outside these attractors are unstable and the network rapidly falls back into the nearest attractor state from them.


A binary spatial decision task in which an animal can go into the left or right arm of a T-shaped arena. It is often used as working memory paradigm, in which the animal must choose either the same or the opposite arm to the one that was chosen in the previous trial.

Morris water maze

A behavioural paradigm in which an animal swims through a water basin to find a hidden platform under the water surface. Visual cues around the maze allow animals to navigate directly to the platform once they have learned the platform location over repeated trials.

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Hainmueller, T., Bartos, M. Dentate gyrus circuits for encoding, retrieval and discrimination of episodic memories. Nat Rev Neurosci 21, 153–168 (2020).

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