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Prefrontal–hippocampal interactions in episodic memory

Key Points

  • The prefrontal cortex (PFC) and hippocampus support complementary functions in episodic memory.

  • Connections between the PFC and the hippocampus are particularly important for episodic memory.

  • In addition, these areas interact bidirectionally through oscillatory synchrony.

  • Distinct types of interactions between the PFC and hippocampus are supported by a direct hippocampus–PFC connection and by bidirectional pathways via intermediaries in the thalamus and perirhinal and lateral entorhinal cortices.

  • This Review outlines a model of how the PFC and hippocampus interact during episodic memory tasks.


The roles of the hippocampus and prefrontal cortex (PFC) in memory processing — individually or in concert — are a major topic of interest in memory research. These brain areas have distinct and complementary roles in episodic memory, and their interactions are crucial for learning and remembering events. Considerable evidence indicates that the PFC and hippocampus become coupled via oscillatory synchrony that reflects bidirectional flow of information. Furthermore, newer studies have revealed specific mechanisms whereby neural representations in the PFC and hippocampus are mediated through direct connections or through intermediary regions. These findings suggest a model of how the hippocampus and PFC, along with their intermediaries, operate as a system that uses the current context of experience to retrieve relevant memories.

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Figure 1: Functions of the prefrontal cortex and the hippocampus in memory.
Figure 2: Indirect and direct prefrontal–hippocampal pathways.
Figure 3: Prefrontal–hippocampal interactions.
Figure 4: A model of prefrontal–hippocampal functional interactions.


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The author acknowledges funding from the US National Institute of Mental Health (grant numbers MH094263, MH051570 and MH052090).

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Correspondence to Howard Eichenbaum.

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The author declares no competing financial interests.

PowerPoint slides


Oscillatory synchrony

Coordination of local field potential oscillations and spiking activity in two connected brain areas. Usually observed as a locking of the phase of oscillatory activity within a specific frequency band.

Recognition memory

The ability to remember stimuli presented earlier, by later correctly recognizing those stimuli and by correctly rejecting other stimuli that were not previously experienced.

Wisconsin Card Sorting Test

A card-sorting task in which participants must switch strategies to sort cards according to different parameters, such as rank, suit or colour.

Nucleus reuniens

(Re). A midline nucleus at the centre of the thalamus that bidirectionally connects the prefrontal cortex with the hippocampus.

Crossed lesions

Unilateral inactivation or lesion of each of two areas in opposing hemispheres, thus leaving each area intact in one hemisphere but eliminating ipsilateral connections between them.

Theta oscillations

Oscillations in the local field potential or spiking activity in the 4–12 Hz frequency band originating in the medial septum.

Local field potentials

Recorded electrical activity patterns that reflect both synaptic potentials and spiking activity of many neighbouring neurons within a brain area. Oscillatory patterns in local field potential reflect synchronous neural activity at particular frequencies.

Phase shifts

Changes in the temporal coordination of spiking activity that, in many brain areas, is closely time-locked to the phase of a particular oscillation in the local field potential.


Oscillations in the local field potential in low (30–80 Hz) or high (80–140 Hz) frequency bands (defined differently among different studies).

Post-learning consolidation

A prolonged period (hours to months) after learning, over which memories that are initially unstable become stable. This process is thought to involve the integration of new episodic memories into a semantic memory network.

Circuit psychiatry

The use of powerful neurobiological tools to identify, monitor and manipulate specific brain circuits to advance knowledge of normal brain function and mental disorders.

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Eichenbaum, H. Prefrontal–hippocampal interactions in episodic memory. Nat Rev Neurosci 18, 547–558 (2017).

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