Dopamine dynamics are dispensable for movement but promote reward responses
成果类型：
Article
署名作者：
Cai, Xintong; Liu, Changliang; Tsutsui-Kimura, Iku; Lee, Joon-Hyuk; Guo, Chong; Banerjee, Aditi; Lee, Jinoh; Amo, Ryunosuke; Xie, Yudi; Patriarchi, Tommaso; Li, Yulong; Watabe-Uchida, Mitsuko; Uchida, Naoshige; Kaeser, Pascal S.
署名单位：
Harvard University; Harvard Medical School; Harvard University; University of Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Zurich; Peking University
刊物名称：
Nature
ISSN/ISSBN：
0028-6432
DOI：
10.1038/s41586-024-08038-z
发表日期：
2024-11-14
关键词：
neurons
release
performance
prediction
proteins
channels
calcium
signals
pattern
absence
摘要：
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. Experiments using conditional RIM1 and RIM2 knockout mice and acute pharmacological manipulations clarify the role of rapid dopamine dynamics, whereby these dynamics are dispensable for movement initiation but important for reward-guided conditioned behaviours.