Ventral tegmental area dopamine neuron activity mediates multi-valent outcomes during decision making under risk of punishment.

Authors

Wonn S Pyon, Omar A Viera-Resto, Mojdeh Faraji, Shelby L Blaes, Caitlin A Orsini, Max S Gotlin, Christos Raptis, Carolina Cruz-Wegener, Azin Behnood-Rod, Brandon M Hellbusch, Sheldon W Joseph, Jacob Barrett, Hannah M Holik, Sarthak M Singhal, Matthew R Burns, Charles J Frazier, Jennifer L Bizon, Barry Setlow

Published in

bioRxiv : the preprint server for biology. Jul 20, 2026. Epub Jul 20, 2026.

Abstract

Dopamine contributes to reward-related decision making, but its contributions to decision contexts that include explicit punishment are less well understood. To elucidate the role of ventral tegmental area (VTA) dopamine neurons in decision making under risk of punishment, we used fiber photometry to record activity in these neurons during a decision-making task in which rats choose between a small, "safe" reward and a large reward associated with varying probabilities of explicit punishment. Dopamine neuron activity exhibited phasic increases during risky "Wins" (reward without punishment) and phasic decreases during risky "Losses" (reward plus punishment), each of which scaled with punishment probability and intensity. Further analyses revealed that this outcome-evoked activity predicted choices on subsequent trials. To determine whether VTA dopamine neuron activity plays a causal role in these risk-based decisions, we used optogenetics to selectively inhibit these neurons during risky Wins and Losses. Inhibition of VTA dopamine neurons during Wins selectively reduced the frequency of risky choices after a Win, whereas inhibition during Losses selectively reduced the frequency of risky choices after a Loss. These data reveal that VTA dopamine neuron activity during outcome receipt is causally related to subsequent decision-making behavior. In addition, the fact that the effects of inhibition on choice behavior were specific to the outcome with which the inhibition was paired suggests that VTA dopamine neuron activity contributes to updating after Wins and Losses independently.
Dopamine is implicated in movement, motivation, and learning, and has been strongly linked with substance use and risk-seeking behavior. Despite these associations, it is unclear how the activity of dopamine neurons influences decision making under risk of punishment. To elucidate this, we recorded from ventral tegmental area (VTA) dopamine neurons and found that their activity at the population level integrates reward alongside the probability and intensity of punishment experienced during risky outcomes. Further, inhibition of VTA dopamine neuron activity during risky outcomes decreased risk-seeking behavior in an outcome-specific manner. Our findings align with models suggesting that VTA dopamine neurons signal prediction errors, and provide insight into the role of these neurons in adaptive decision making.

PMID:
42539269
Bibliographic data and abstract were imported from PubMed on 01 Aug 2026.

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