Dopamine dynamics during stimulus-reward learning in mice can be explained by performance rather than learning

Konstantin Bakhurin, Ryan N. Hughes, Qiaochu Jiang, Meghdoot Hossain, Boris Gutkin, Isabella P. Fallon and Henry H. Yin ()
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Konstantin Bakhurin: Duke University
Ryan N. Hughes: Duke University
Qiaochu Jiang: Duke University
Meghdoot Hossain: PSL Université
Boris Gutkin: PSL Université
Isabella P. Fallon: Duke University School of Medicine
Henry H. Yin: Duke University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract The reward prediction error (RPE) hypothesis posits that phasic dopamine (DA) activity in the ventral tegmental area (VTA) encodes the difference between expected and actual rewards to drive reinforcement learning. However, emerging evidence suggests DA may instead regulate behavioral performance. Here, we used force sensors to measure subtle movements in head-fixed mice during a Pavlovian stimulus-reward task, while recording and manipulating VTA DA activity. We identified distinct DA neuron populations tuned to forward and backward force exertion. They are active during both spontaneous and conditioned behaviors, independent of learning or reward predictability. Variations in force and licking fully account for DA dynamics traditionally attributed to RPE, including variations in firing rates related to reward magnitude, probability, and omission. Optogenetic manipulations further confirmed that DA modulates force exertion and behavioral transitions in real time, without affecting learning. Our findings challenge the RPE hypothesis and instead suggest that VTA DA neurons dynamically adjust the gain of motivated behaviors, controlling their latency, direction, and intensity during performance.

Date: 2025
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DOI: 10.1038/s41467-025-64132-4

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