Dopamine release at the time of a predicted aversive outcome causally controls the trajectory and expression of conditioned behavior.
Dopamine release at the time of a predicted aversive outcome causally controls the trajectory and expression of conditioned behavior.
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DOI：
10.1016/j.celrep.2023.112948
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发表时间：
2023-08-29
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
多巴胺释放在丘脑核（NAc）是因果关系与适应性厌恶学习，其失调是焦虑和应激障碍的核心表型。在这里，我们记录了NAc核心多巴胺在一项任务中，小鼠学习区分两种类型的结果信号的线索：（1）脚电击介绍和（2）脚电击遗漏。我们发现，多巴胺的释放是由足电遗漏引起的。这种多巴胺反应在遗漏是意料之外的时候最大，并在学习过程中减少，人为地增加这种信号会破坏辨别学习。相反，光遗传学抑制多巴胺对电击脚本身的反应会损害学习。最后，理论驱动的计算模型表明，这些影响可以解释为多巴胺信号的预测厌恶事件的感知显着性。总之，我们阐明了NAc多巴胺在厌恶性学习中的作用，并为理解焦虑和应激障碍的神经机制提供了潜在的途径。Kutlu等联合收割机在小鼠中结合了一系列光学和计算方法，以确定多巴胺释放如何响应厌恶刺激控制学习。他们发现多巴胺与事件的显著性成比例，当预测到遗漏时，足电击遗漏引起的多巴胺释放较少。
Dopamine release in the nucleus accumbens (NAc) is causally linked to adaptive aversive learning, and its dysregulation is a core phenotype in anxiety and stress disorders. Here, we record NAc core dopamine during a task where mice learn to discriminate between cues signaling two types of outcomes: (1) footshock presentation and (2) footshock omission. We show that dopamine release is evoked by footshock omission. This dopamine response is largest when the omission is unexpected and decreases over learning, and artificially increasing this signal disrupts discrimination learning. Conversely, optogenetic inhibition of dopamine responses to the footshock itself impairs learning. Finally, theory-driven computational modeling suggests that these effects can be explained by dopamine signaling the perceived saliency of predicted aversive events. Together, we elucidate the role of NAc dopamine in aversive learning and offer potential avenues for understanding the neural mechanisms involved in anxiety and stress disorders. Kutlu et al. combine a range of optical and computational approaches in mice to define how dopamine release in response to aversive stimuli controls learning. They find that dopamine scales with the saliency of events and that less dopamine release is evoked by footshock omission when the omission is predicted.
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