Romero Pinto Sandra, Uchida Naoshige
Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, MA, USA.
Program in Speech and Hearing Bioscience and Technology, Division of Medical Sciences, Harvard Medical School, Boston, MA, USA.
Nat Commun. 2025 Aug 13;16(1):7529. doi: 10.1038/s41467-025-62280-1.
A hallmark of various psychiatric disorders is biased future predictions. Here we examined the mechanisms for biased value learning using reinforcement learning models incorporating recent findings on synaptic plasticity and opponent circuit mechanisms in the basal ganglia. We show that variations in tonic dopamine can alter the balance between learning from positive and negative reward prediction errors, leading to biased value predictions. This bias arises from the sigmoidal shapes of the dose-occupancy curves and distinct affinities of D1- and D2-type dopamine receptors: changes in tonic dopamine differentially alters the slope of the dose-occupancy curves of these receptors, thus sensitivities, at baseline dopamine concentrations. We show that this mechanism can explain biased value learning in both mice and humans and may also contribute to symptoms observed in psychiatric disorders. Our model provides a foundation for understanding the basal ganglia circuit and underscores the significance of tonic dopamine in modulating learning processes.
各种精神疾病的一个标志是有偏差的未来预测。在这里,我们使用强化学习模型研究了有偏差的价值学习机制,该模型纳入了基底神经节中突触可塑性和对抗回路机制的最新发现。我们表明,持续性多巴胺的变化可以改变从正向和负向奖励预测误差中学习的平衡,从而导致有偏差的价值预测。这种偏差源于剂量-占有率曲线的S形以及D1型和D2型多巴胺受体的不同亲和力:在基线多巴胺浓度下,持续性多巴胺的变化会不同程度地改变这些受体的剂量-占有率曲线的斜率,进而改变敏感性。我们表明,这种机制可以解释小鼠和人类中有偏差的价值学习,并且可能也导致了在精神疾病中观察到的症状。我们的模型为理解基底神经节回路提供了基础,并强调了持续性多巴胺在调节学习过程中的重要性。