Dopamine dynamics are dispensable for movement but promote reward responses

Xintong Cai, Changliang Liu, Iku Tsutsui-Kimura, Joon-Hyuk Lee, Chong Guo, Aditi Banerjee, Jinoh Lee, Ryunosuke Amo, Yudi Xie, Tommaso Patriarchi, Yulong Li, Mitsuko Watabe-Uchida, Naoshige Uchida and Pascal S. Kaeser ()
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Xintong Cai: Harvard Medical School
Changliang Liu: Harvard Medical School
Iku Tsutsui-Kimura: Harvard University
Joon-Hyuk Lee: Harvard Medical School
Chong Guo: Harvard Medical School
Aditi Banerjee: Harvard Medical School
Jinoh Lee: Harvard Medical School
Ryunosuke Amo: Harvard University
Yudi Xie: Harvard University
Tommaso Patriarchi: University of Zurich
Yulong Li: Peking University School of Life Sciences
Mitsuko Watabe-Uchida: Harvard University
Naoshige Uchida: Harvard University
Pascal S. Kaeser: Harvard Medical School

Nature, 2024, vol. 635, issue 8038, 406-414

Abstract: Abstract Dopamine signalling modes differ in kinetics and spatial patterns of receptor activation1,2. How these modes contribute to motor function, motivation and learning has long been debated3–21. Here we show that action-potential-induced dopamine release is dispensable for movement initiation but supports reward-oriented behaviour. We generated mice with dopamine-neuron-specific knockout of the release site organizer protein RIM to disrupt action-potential-induced dopamine release. In these mice, rapid in vivo dopamine dynamics were strongly impaired, but baseline dopamine persisted and fully supported spontaneous movement. Conversely, reserpine-mediated dopamine depletion or blockade of dopamine receptors disrupted movement initiation. The dopamine precursor l-DOPA reversed reserpine-induced bradykinesia without restoring fast dopamine dynamics, a result that substantiated the conclusion that these dynamics are dispensable for movement initiation. In contrast to spontaneous movement, reward-oriented behaviour was impaired in dopamine-neuron-specific RIM knockout mice. In conditioned place preference and two-odour discrimination tasks, the mice effectively learned to distinguish the cues, which indicates that reward-based learning persists after RIM ablation. However, the performance vigour was reduced. During probabilistic cue-reward association, dopamine dynamics and conditioned responses assessed through anticipatory licking were disrupted. These results demonstrate that action-potential-induced dopamine release is dispensable for motor function and subsecond precision of movement initiation but promotes motivation and performance during reward-guided behaviours.

Date: 2024
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DOI: 10.1038/s41586-024-08038-z

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