# Dentate Gyrus Engrams in Fear and Reward: Mechanistic Principles, Critical Gaps, and Paths to Translation

## TL;DR

The dentate gyrus can link contexts to both fear and reward memories, making it a key target for treating disorders like addiction and PTSD.

## Contribution

Highlights the DG's unique plasticity in encoding opposing emotional memories and identifies gaps in reward engram research for psychiatric applications.

## Key findings

- DG encodes both fear and reward memories in overlapping circuits with context-dependent plasticity.
- Reward engrams involve distributed brain regions like the nucleus accumbens and prefrontal cortex.
- DG's flexible valence encoding distinguishes it from regions with fixed emotional coding.

## Abstract

The hippocampal dentate gyrus (DG) has emerged as a cornerstone of engram research. While DG fear‐based engrams have been extensively studied, revealing principles of allocation, consolidation, retrieval, and valence switching, engrams encoding context‐reward associations, particularly those involving drugs of abuse, remain comparatively underexplored. This knowledge gap has critical implications for understanding addiction, depression, and other disorders involving dysfunctional reward processing. In this review, we first establish the DG's unique anatomical and functional properties that position it as an ideal model system for engram research. We then systematically examine the DG fear engram literature, documenting how decades of contextual fear conditioning studies have elucidated mechanisms of competitive allocation, molecular consolidation, competing extinction ensembles, and context‐dependent discrimination versus generalization. Turning to reward engrams, we synthesize emerging evidence demonstrating that drug‐context associations are encoded through sparse, distributed ensembles across multiple brain regions including the nucleus accumbens, prefrontal cortex, amygdala, and hippocampus. While these studies establish foundational principles of reward engram allocation and retrieval, critical mechanistic gaps remain, particularly regarding differences between drug‐associated and natural reward memories, the neural coding of context versus valence in hippocampal circuits, and the mechanisms underlying drug associated reward memory extinction. Evidence from valence switching studies demonstrates that the DG processes and stores both fear and reward memories within overlapping circuits, exhibiting remarkable plasticity in linking contextual representations to opposing emotional outcomes, a flexibility distinguishing it from structures with hardwired valence encoding. This encoding capacity positions the DG as a promising target for interventions aimed at modifying pathological emotional associations in addiction and trauma‐related disorders while preserving contextual specificity. Understanding reward engram mechanisms with the same rigor applied to fear engrams is essential for developing comprehensive frameworks of how DG circuits contribute to memory‐related psychopathology and for translating engram research into therapeutic applications.

Memories of rewarding experiences powerfully shape behavior, yet when maladaptive, they can drive psychiatric conditions including addiction, depression, and PTSD. Memory traces, or engrams, have been extensively studied for fear memories in the hippocampal dentate gyrus. However, engrams for rewarding experiences remain comparatively underexplored, a significant gap given that many psychiatric conditions involve disrupted reward processing. This review compares fear and reward engram research, identifying critical knowledge gaps. Importantly, the dentate gyrus can flexibly reassociate contexts with different emotional outcomes, unlike brain regions with fixed emotional coding. This plasticity positions it as a promising therapeutic target for memory‐related psychiatric disorders.