Nigrostriatal dopamine signals sequence-specific action-outcome prediction errors.
Nigrostriatal dopamine signals sequence-specific action-outcome prediction errors.
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DOI：
10.1016/j.cub.2021.09.040
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发表时间：
2021-12-06
期刊：
影响因子：
--
通讯作者：
Jin X
中科院分区：
文献类型：
--
作者：
Hollon NG;Williams EW;Howard CD;Li H;Traut TI;Jin X
多巴胺被认为是巴甫洛夫条件反射过程中对线索-奖励预测错误的编码，它发出的信号是线索预测的实际奖励与预期奖励之间的差异。虽然这一理论已被广泛应用于有关工具性行为的强化学习，但多巴胺是否代表行为结果预测错误以及它如何控制序列行为仍然是未知的。事实上，绝大多数以前研究多巴胺反应的研究主要使用离散的奖励-预测刺激，无论是不需要任何行动来获得奖励的巴甫洛夫条件刺激，还是基本上指导动物如何以及何时对奖励做出反应的显式辨别刺激。在这里，通过训练小鼠进行光遗传颅内自我刺激，我们研究了自我发起的目标导向行为如何影响黑质纹状体多巴胺传输过程中的单一以及顺序的工具行动，在行为环境中，动物的外部环境的明显变化最小。我们发现，由直接光遗传学刺激诱发的多巴胺释放在作为动物自身行为的结果递送时显著减少，相对于非偶然的被动刺激。这种多巴胺抑制一般化的食物奖励，是具体的加强行动，暂时限制抵消预期的结果，并表现出序列选择性与层次控制的顺序行为。总之，这些发现表明，黑质纹状体多巴胺信号序列特异性预测错误的行动结果协会，与强化学习和工具行为的健康和疾病的基本影响。多巴胺在线索奖励情境中发出预测错误的信号。在这里，Hollon等人表明，当奖励结果是自我发起行动的预期结果时，黑质纹状体多巴胺会受到抑制。这些动作结果预测错误甚至抑制了光遗传学刺激的多巴胺，并在动作序列中表现出分层控制。
Dopamine has been suggested to encode cue-reward prediction errors during Pavlovian conditioning, signaling discrepancies between actual versus expected reward predicted by the cues. While this theory has been widely applied to reinforcement learning concerning instrumental actions, whether dopamine represents action-outcome prediction errors and how it controls sequential behavior remain largely unknown. Indeed, the vast majority of previous studies examining dopamine responses primarily have used discrete reward-predictive stimuli, whether Pavlovian conditioned stimuli for which no action is required to earn reward, or explicit discriminative stimuli that essentially instruct an animal how and when to respond for reward. Here, by training mice to perform optogenetic intracranial self-stimulation, we examined how self-initiated goal-directed behavior influences nigrostriatal dopamine transmission during single as well as sequential instrumental actions, in behavioral contexts with minimal overt changes in the animal’s external environment. We found that dopamine release evoked by direct optogenetic stimulation was dramatically reduced when delivered as the consequence of the animal’s own action, relative to non-contingent passive stimulation. This dopamine suppression generalized to food rewards, was specific to the reinforced action, was temporally restricted to counteract the expected outcome, and exhibited sequence-selectivity consistent with hierarchical control of sequential behavior. Together these findings demonstrate that nigrostriatal dopamine signals sequence-specific prediction errors in action-outcome associations, with fundamental implications for reinforcement learning and instrumental behavior in health and disease. Dopamine signals prediction errors in cued-reward contexts. Here, Hollon et al. show that nigrostriatal dopamine is inhibited when a reward outcome is the expected consequence of self-initiated action. These action-outcome prediction errors suppress even optogenetically stimulated dopamine and exhibit hierarchical control during action sequences.
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