Mesolimbic dopamine dynamically tracks, and is causally linked to, discrete aspects of value-based decision making.
Mesolimbic dopamine dynamically tracks, and is causally linked to, discrete aspects of value-based decision making.
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DOI：
10.1016/j.biopsych.2014.10.024
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发表时间：
2015-05-15
影响因子：
10.6
通讯作者：
Carelli RM
中科院分区：
文献类型：
--
作者：
Saddoris MP;Sugam JA;Stuber GD;Witten IB;Deisseroth K;Carelli RM
为了做出适当的选择，生物体必须权衡潜在有价值结果的成本和收益，这一过程涉及伏隔核（NAc）及其多巴胺能输入。然而，目前尚不清楚多巴胺是否随着行为偏好的改变而动态跟踪预期奖励价值的变化，如果是这样，它是否与奖励大小和/或强化延迟等特定价值组成部分有因果关系。电化学方法用于测量延迟折扣任务（n=7只大鼠）中亚秒NAc多巴胺的释放，其中延迟折扣任务的大小是固定的，但延迟在不同区块之间变化。接下来，为了评估这种多巴胺信号是否与选择行为的特定组成部分有因果关系，我们使用改进的延迟折扣任务对NAc中的多巴胺末端进行选择性光遗传刺激，其中延迟和大小独立变化（n=23只大鼠）。预测可用选择的线索诱发了多巴胺的释放，多巴胺的释放随大鼠偏好的选择而变化，并随着大奖励的延迟和强化的增加而动态变化。在第二个实验中，多巴胺信号与决策特征有因果关系，因为在预测提示呈现期间，光遗传学增强的NAc内多巴胺释放足以改变随后的价值相关选择。重要的是，这种多巴胺介导的选择转变仅限于基于延迟的决策，而不是基于大小的决策。这些发现表明，NAc多巴胺动态跟踪延迟折扣，并在基于价值的关联策略子集中建立了这种信号的因果作用。
To make appropriate choices, organisms must weigh the costs and benefits of potential valuable outcomes, a process known to involve the nucleus accumbens (NAc) and its dopaminergic input. However, it is currently unknown if dopamine dynamically tracks alterations in expected reward value `on-line' as behavioral preferences change, and if so, if it is causally linked to specific components of value such as reward magnitude and/or delay to reinforcement. Electrochemical methods were used to measure subsecond NAc dopamine release during a delay discounting task where magnitude was fixed but delay varied across blocks (n=7 rats). Next, to assess whether this dopamine signaling was causally related to specific components of choice behavior, we employed selective optogenetic stimulation of dopamine terminals in the NAc using a modified delay discounting task in which both delay and magnitude varied independently (n=23 rats). Cues predictive of available choices evoked dopamine release that scaled with the rat's preferred choices, and dynamically shifted as delay to reinforcement for the large reward increased. In the second experiment, dopamine signaling was causally related to features of decision making, as optogenetically-enhanced dopamine release within the NAc during predictive cue presentation was sufficient to alter subsequent value-related choices. Importantly, this dopamine-mediated shift in choice was limited to delay-based, but not magnitude-based decisions. These findings indicate that NAc dopamine dynamically tracks delay discounting, and establishes a causal role for this signaling in a subset of value-based associative strategies.
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