Magnard Robin, Cheng Yifeng, Zhou Joanna, Province Haley, Thiriet Nathalie, Janak Patricia H, Vandaele Youna
Department of Psychological and Brain Sciences, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD.
Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD.
bioRxiv. 2025 Jan 11:2024.10.16.618735. doi: 10.1101/2024.10.16.618735.
Mesolimbic dopamine (DA) neurons are central to sequence learning and habit formation. Yet, the mechanisms by which cue-induced DA neural activity drives goal-directed or habitual sequence execution remain unknown. We designed two novel tasks to investigate how sequence initiation and termination cues influence DA-driven behavioral strategies and learning. We found that sequence initiation and termination cues differentially affect reward expectation during action sequences, with only the termination cue contributing to greater outcome devaluation insensitivity, automaticity and behavioral chunking. Mesolimbic fiber photometry recording revealed that this habit-like behavior was associated with a rapid backpropagation in DA signals from the reward to the immediately preceding cue and with attenuated DA reward prediction error signals, which reflected greater behavioral inflexibility. Finally, in absence of external cues, brief optogenetic stimulation of VTA DA neurons at sequence termination was sufficient to drive automaticity and behavioral chunking. Our results highlight the critical role of cue-evoked DA signals at sequence termination in mediating credit assignment and driving the development of habitual action sequence execution.
中脑边缘多巴胺（DA）神经元对于序列学习和习惯形成至关重要。然而，线索诱导的DA神经活动驱动目标导向或习惯性序列执行的机制仍不清楚。我们设计了两项新任务，以研究序列起始和终止线索如何影响DA驱动的行为策略和学习。我们发现，序列起始和终止线索在动作序列中对奖励期望有不同影响，只有终止线索会导致更大的结果贬值不敏感性、自动性和行为组块化。中脑边缘纤维光度记录显示，这种类似习惯的行为与DA信号从奖励到紧接在前的线索的快速反向传播以及减弱的DA奖励预测误差信号有关，这反映了更大的行为不灵活性。最后，在没有外部线索的情况下，在序列终止时对腹侧被盖区DA神经元进行短暂的光遗传学刺激足以驱动自动性和行为组块化。我们的结果突出了序列终止时线索诱发的DA信号在介导信用分配和驱动习惯性动作序列执行发展中的关键作用。
