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纹状体多巴胺在动态区域尺度上代表效价。

Striatal dopamine represents valence on dynamic regional scales.

作者信息

Bornhoft Kaisa N, Prohofsky Julianna, O'Neal Timothy J, Wolff Amy R, Saunders Benjamin T

机构信息

Department of Neuroscience, University of Minnesota.

Medical Discovery Team on Addiction, University of Minnesota.

出版信息

J Neurosci. 2025 Mar 17;45(17). doi: 10.1523/JNEUROSCI.1551-24.2025.

Abstract

Adaptive decision making relies on dynamic updating of learned associations where environmental cues come to predict valenced stimuli, such as food or threat. Cue-guided behavior depends on a network of brain systems, including dopaminergic projections to the striatum. Critically, it remains unclear how dopamine signaling across the striatum encodes multi-valent, dynamic learning contexts, where positive and negative associations must be rapidly disambiguated. To understand this, we employed a Pavlovian discrimination paradigm, where cues predicting food or threat were intermingled during conditioning sessions, and their meaning was serially reversed across training. We found that male and female rats readily distinguished these cues and updated their behavior rapidly upon valence reversal. Using fiber photometry, we recorded dopamine signaling in three major striatal subregions - the dorsolateral striatum (DLS), the nucleus accumbens (NAc) core, and the nucleus accumbens medial shell - finding that valence was represented uniquely across all three regions, indicative of local signals biased for value and salience. Further, ambiguity introduced by cue reversals reshaped striatal dopamine on different timelines: nucleus accumbens signals updated more readily than those in the DLS. Together, these results indicate that striatal dopamine flexibly encodes stimulus valence according to region-specific rules, and these signals are dynamically modulated by changing contingencies in the resolution of ambiguity about the meaning of environmental cues. Adaptive decision making relies on updating learned associations to disambiguate predictions of reward or threat. This cue-guided behavior depends on striatal dopamine, but it remains unclear how dopamine signaling encodes multi-valent, dynamic learning contexts. Here, we employed a paradigm where cues predicting positive and negative outcomes were intermingled, and their meaning was serially reversed across time. We recorded dopamine signaling, finding heterogeneous patterns of valence encoding across striatal subregions, and cue reversal reshaped subregional signals on different timelines. Our results suggest that dopamine flexibly encodes dynamic learning contexts to resolve ambiguity about the meaning of environmental cues.

摘要

适应性决策依赖于对习得关联的动态更新,其中环境线索开始预测有价值的刺激,如食物或威胁。线索引导的行为依赖于一个脑系统网络,包括向纹状体的多巴胺能投射。至关重要的是,目前尚不清楚整个纹状体的多巴胺信号如何编码多价、动态的学习情境,在这种情境中,正负关联必须迅速区分。为了理解这一点,我们采用了一种巴甫洛夫辨别范式,在条件反射训练过程中,预测食物或威胁的线索相互交织,并且它们的含义在训练过程中依次反转。我们发现雄性和雌性大鼠能够轻松区分这些线索,并在效价反转时迅速更新它们的行为。使用光纤光度法,我们记录了三个主要纹状体亚区域——背外侧纹状体(DLS)、伏隔核(NAc)核心和伏隔核内侧壳——的多巴胺信号,发现效价在所有三个区域都有独特的表征,表明局部信号偏向于价值和显著性。此外,线索反转引入的模糊性在不同的时间尺度上重塑了纹状体多巴胺:伏隔核的信号比DLS中的信号更容易更新。总之,这些结果表明,纹状体多巴胺根据区域特异性规则灵活地编码刺激效价,并且这些信号在解决环境线索含义的模糊性时,会随着变化的偶然性而动态调节。适应性决策依赖于更新习得的关联,以消除对奖励或威胁的预测的歧义。这种线索引导的行为依赖于纹状体多巴胺,但尚不清楚多巴胺信号如何编码多价、动态的学习情境。在这里,我们采用了一种范式,其中预测正负结果的线索相互交织,并且它们的含义随时间依次反转。我们记录了多巴胺信号,发现整个纹状体亚区域的效价编码模式各异,并且线索反转在不同的时间尺度上重塑了亚区域信号。我们的结果表明,多巴胺灵活地编码动态学习情境,以解决环境线索含义的模糊性。

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