A role for prefrontal dopamine signaling in control of goal-directed actions

Petitbon, A.; Contini, A.; Walle, R.; Allichon, M.-C.; Hardt, L.; Ducrocq, F.; Couty, P.; Oummadi, A.; Angelo, M.-F.; Delcasso, S.; Cazala, M.; Depret, M.; Harouna, Y.; Ilie, A.; Acedo, F.; Correa-Vazquez, J.; Ortole, R.; Thebeaud, R.; Blanc, A.; Rousseaud, M.; Andrianarivelo, A.; Ferreira, G.; Barik, J.; Vanhoutte, P.; Trifilieff, P.

doi:10.1101/2025.10.10.681663

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bioRxiv · 10.1101/2025.10.10.681663

A role for prefrontal dopamine signaling in control of goal-directed actions

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Abstract

Impairments in behavioral flexibility commonly found across psychiatric disorders have often been attributed to a dysfunction of the medial prefrontal cortex (mPFC), notably in relation with altered dopamine transmission. However, how dopamine transmission shapes neuronal activity in the mPFC to allow adapting to a changing situation remains largely elusive. Here, we show that dopamine dynamics in the mPFC encode the value of instrumental actions, in particular during reversal learning. Such signal shapes the activity of mPFC dopaminoceptive neurons during reversal learning through the recruitment of heteromers formed by dopamine D1 and D2 receptors with NMDA receptors. In accordance, blockade of either D1/NMDA or D2/NMDA heteromers in the mPFC selectively impairs reversal of outcome identities but not learning and expression of initial action-outcome associations. Our findings provide mechanistic evidence for a central role of dopamine in the mPFC to allow updating goal-directed actions.

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Petitbon, A., Contini, A., Walle, R., Allichon, M.-C., Hardt, L., Ducrocq, F., Couty, P., Oummadi, A., Angelo, M.-F., Delcasso, S., Cazala, M., Depret, M., Harouna, Y., Ilie, A., Acedo, F., Correa-Vazquez, J., Ortole, R., Thebeaud, R., Blanc, A., Rousseaud, M., Andrianarivelo, A., Ferreira, G., Barik, J., Vanhoutte, P., Trifilieff, P.. 2025-10-12. A role for prefrontal dopamine signaling in control of goal-directed actions. https://doi.org/10.1101/2025.10.10.681663

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