Mesostriatal dopamine is sensitive to changes in specific cue-reward contingencies

Learning causal relationships relies on understanding how often one event precedes another. To gain an understanding of how dopamine neuron activity and neurotransmitter release change when a retrospective relationship is degraded for a specific pair of events, we used outcome-selective Pavlovian contingency degradation in rats. Two cues were paired with distinct food rewards, one of which was also delivered in the absence of either cue. Conditioned responding was attenuated for the cue-reward contingency that was degraded. Dopamine neuron activity in the midbrain and dopamine release in the ventral striatum in response to the cue and subsequent reward were attenuated during degraded versus non-degraded trials, and contingency degradation also abolished the trial-by-trial history dependence of dopamine responses at the time of trial outcome. This profile of changes in cue- and reward-evoked responding is not easily explained by a standard reinforcement learning model. An alternative model based on learning causal relationships was better able to capture evoked dopamine responses during contingency degradation, as well as conditioned behavior following optogenetic manipulations of dopamine during noncontingent rewards. Our results suggest that mesostriatal dopamine encodes the contingencies between meaningful events during learning.

因果关系的学习，有赖于探明某一事件相较于另一事件的先行发生频次。为探明当特定事件对的回溯性因果关系被削弱时，多巴胺神经元活动与神经递质释放会发生何种变化，我们在大鼠实验中采用了结果选择性巴甫洛夫条件联结降解范式（outcome-selective Pavlovian contingency degradation）。我们设置了两种线索，分别与不同的食物奖赏绑定，且其中一种奖赏还可在无任何线索呈现的情况下单独给予。经削弱的线索-奖赏条件联结对应的条件性反应出现了减弱。相较于未受削弱的试次，受削弱试次中，中脑多巴胺神经元活动与腹侧纹状体（ventral striatum）的多巴胺释放（对应线索及后续奖赏刺激）均出现减弱；同时，条件联结降解还消除了试次结果出现时多巴胺反应的逐试次历史依赖性。这种线索与奖赏诱发反应的变化特征，难以通过标准强化学习模型加以解释。一种基于因果关系学习的替代模型，能够更好地拟合条件联结降解范式下的诱发型多巴胺反应，以及非联结奖赏条件下对多巴胺进行光遗传学操控（optogenetic manipulation）后的条件性行为。本研究结果表明，中脑纹状体多巴胺系统会对学习过程中具有意义的事件间的条件联结进行编码。