A flexible hippocampal population code for experience relative to reward

New findings suggest the same brain systems that guide animals to rewards may be weakened in dementia and intensified in addiction.¹

nature.com/articles/s41593-025-01985-4

Abstract

To reinforce rewarding behaviors, events leading up to and following rewards must be remembered. Hippocampal place cell activity spans spatial and non-spatial episodes, but whether hippocampal activity encodes entire sequences of events relative to reward is unknown. Here, to test this possibility, we performed two-photon imaging of hippocampal CA1 as mice navigated virtual environments with changing hidden reward locations. We found that when the reward moved, a subpopulation of neurons updated their firing fields to the same relative position with respect to reward, constructing behavioral timescale sequences spanning the entire task. Over learning, this reward-relative representation became more robust as additional neurons were recruited, and changes in reward-relative firing often preceded behavioral adaptations following reward relocation. Concurrently, the spatial environment code was maintained through a parallel, dynamic subpopulation rather than through dedicated cell classes. These findings reveal how hippocampal ensembles flexibly encode multiple aspects of experience while amplifying behaviorally relevant information.

Footnotes

1. news.stanford.edu/stories/2025/06/neural-maps-brain-reward-research-dementia-addiction ↩