Faculty, Staff and Student Publications

Language

English

Publication Date

11-22-2025

Journal

Nature Communications

DOI

10.1038/s41467-025-65347-1

PMID

41274918

PMCID

PMC12660755

PubMedCentral® Posted Date

11-22-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Flexibly adjusting food-seeking behaviour in response to food-associated cues and internal states is crucial for animals' survival. However, the neural mechanisms that modulate cued food-seeking behaviour during varying metabolic (i.e., hungry vs. satiated) and emotional (i.e., safe vs. threatened) states remain elusive. Here, we show that the encoding of metabolic or threat states in projection-defined neurons in the prelimbic cortex (PL) mediates cued food-seeking responses in rats. Using microendoscopic imaging, we demonstrate that neural population dynamics in PL consistently represent food cues, task-relevant behaviours, and internal state changes by recruiting distinct subsets of cue-responsive neurons at each state. Single-unit recording and loss-of-function experiments reveal that activity in divergent PL projections to the anterior paraventricular nucleus of the thalamus (aPVT) or the nucleus accumbens (NAc) promotes either hedonic feeding during satiation or food-seeking suppression during threat, respectively. Together, our findings uncover a mechanism by which divergent PL circuits regulate cued food-seeking under distinct metabolic or emotional states.

Keywords

Animals, Prefrontal Cortex, Cues, Male, Feeding Behavior, Rats, Neurons, Emotions, Nucleus Accumbens, Satiation, Neural Pathways, Motivation, Reward

Published Open-Access

yes

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