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Functional bipartition of medial prefrontal cortex into salience detection and movement gain

Hou, S.; Ramirez, L. A.; Mitten, E. H.; Wiaderkiewicz, J.; Narvaez Guzman, M.; Wang, H.; Glover, E. J.

2026-03-20 neuroscience
10.64898/2026.03.18.712525 bioRxiv
Show abstract

Reward prediction error (RPE) is a key function putatively realized by brain-wide neural states to drive learning and adaptive responding. The medial prefrontal cortex (mPFC) is among the many areas implicated in RPE computation. Yet, whether mPFC RPE processing differs as a function of valence, value, and sign is not well-understood. Here, we performed in vivo mPFC calcium imaging in rats engaged in an appetitive or aversive Pavlovian task designed to elicit RPE, along with continuous, unbiased behavioral monitoring. We found that short-latency bulk mPFC activity encodes salience independent of valence, value, or RPE. Surprisingly, as subsequently validated with in vivo bidirectional optogenetics, we show that salience-null mPFC activity modulates generalized movement in a valence- and task-agnostic fashion. Together, these results challenge region-wide RPE encoding by the mPFC, and instead, support a functional bipartition schema combining reactive detection of integrated salience and dynamic modulation of movement gain.

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