Prefrontal neural geometry of learned cues guides motivated behaviours

Winke N(1)(2)(3), Lüthi A(3)(4), Herry C(5)(6), Jercog D(7)(8).

Author information:
(1)INSERM, Neurocentre Magendie, U1215, Bordeaux, France.
(2)Univ. Bordeaux, Neurocentre Magendie, U1215, Bordeaux, France.
(3)Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
(4)University of Basel, Basel, Switzerland.
(5)INSERM, Neurocentre Magendie, U1215, Bordeaux, France. .
(6)Univ. Bordeaux, Neurocentre Magendie, U1215, Bordeaux, France.
.
(7)Univ. Bordeaux, Neurocentre Magendie, U1215, Bordeaux, France.
.
(8)Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark.
.

Animals continuously evaluate their surroundings to decide whether to approach
rewarding opportunities or avoid potential threats. Assigning the appropriate
importance to environmental stimuli is not only crucial for survival but also
underlies complex forms of goal-directed behaviour that are shared across
species, including humans1-4. Understanding how the brain translates such
sensory cues into motivated behaviours is, therefore, central to neuroscience
and psychology. The dorsomedial prefrontal cortex (dmPFC) is a critical
structure that bridges relevant environmental stimuli to goal-directed
behaviour. Salience, valence and value are key dimensions defining stimulus
relevance, but how the dmPFC processes and organizes such dimensions to drive
motivated behaviour remains unclear. Here we monitored single-neuron populations
in the dmPFC using calcium imaging in freely moving male mice while
discriminating between stimuli predicting different reward or punishment
outcomes, which enabled an unprecedented dissociation of salience, valence and
value information. We found that dmPFC populations primarily encode appetitive
and aversive values of learned stimuli and that subpopulations encode valence
and salience along orthogonal information axes. Our results highlight a
concurrent multifaceted population coding of value, salience and valence of
stimuli during associative learning within dmPFC networks, such that the
geometry of dmPFC neuronal representations dynamically shapes appetitive and
aversive motivated behaviours.

© 2026. The Author(s), under exclusive licence to Springer Nature Limited.

DOI: 10.1038/s41586-025-09902-2
PMID: 41501468

Conflict of interest statement: Competing interests: The authors declare no
competing interests.

Auteurs Bordeaux Neurocampus