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基底外侧杏仁核多巴胺传递非联想性情绪显著性信号。

Basolateral amygdala dopamine transmits a nonassociative emotional salience signal.

作者信息

Brickner Megan A, Szot William E, Wolff Amy R, Thomas Mark J, 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

bioRxiv. 2025 May 16:2025.05.15.654323. doi: 10.1101/2025.05.15.654323.

DOI:10.1101/2025.05.15.654323
PMID:40463175
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12132325/
Abstract

Adaptive decision making relies on proper discrimination and prediction of positive and negative events. The basolateral amygdala (BLA) is central to this valence encoding, assigning emotional value to stimuli to drive appropriate behavioral responses. The ventral tegmental area (VTA), which is classically known to regulate associative learning and incentive motivation via dopamine projections to the striatum, also contains strong dopamine projections to the BLA, but this system has received much less attention. Here, we investigated how BLA dopamine signaling is engaged durning learning. We show that reward cues evoke BLA dopamine signals that diminish, rather than grow, with training. As the complexity of the learning context was increased, where rats actively differentiated between various cue types signaling threat, reward, safety, and neutral associations, the magnitude of cue-evoked BLA dopamine responses was largest early in training and reported the level of perceived emotional saliency. Fear and safety cues prompted larger, sustained dopamine signals compared to reward and neutral cues, an effect that was more apparent in female rats, compared to males. Together, our findings broaden the theoretical landscape of dopamine heterogeneity, showing that BLA dopamine supports dynamic disambiguation of relative stimulus importance by non-associatively encoding sensory state transitions, independent of value. These signals reflect a scalar readout of emotional salience to prime, rather than track, learning.

摘要

适应性决策依赖于对积极和消极事件的正确辨别与预测。基底外侧杏仁核(BLA)对于这种效价编码至关重要,它赋予刺激以情感价值,从而驱动适当的行为反应。腹侧被盖区(VTA),传统上已知其通过向纹状体投射多巴胺来调节联想学习和动机激励,它也有强大的多巴胺投射到BLA,但该系统受到的关注要少得多。在此,我们研究了在学习过程中BLA多巴胺信号是如何被激活的。我们发现奖励线索会引发BLA多巴胺信号,随着训练,这些信号会减弱而非增强。随着学习情境复杂性的增加,即大鼠积极区分各种信号威胁、奖励、安全和中性关联的线索类型时,线索引发的BLA多巴胺反应的幅度在训练早期最大,并反映了感知到的情感显著性水平。与奖励和中性线索相比,恐惧和安全线索会引发更大、更持续的多巴胺信号,与雄性大鼠相比,这种效应在雌性大鼠中更明显。总之,我们的研究结果拓宽了多巴胺异质性的理论视野,表明BLA多巴胺通过非联想性地编码感觉状态转换来支持对相对刺激重要性的动态辨别,而与价值无关。这些信号反映了情感显著性的标量读数,用于启动而非跟踪学习。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2508/12132325/9944935c1afb/nihpp-2025.05.15.654323v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2508/12132325/0840b2f61424/nihpp-2025.05.15.654323v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2508/12132325/9a21c955d5e1/nihpp-2025.05.15.654323v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2508/12132325/baa60c02a7c5/nihpp-2025.05.15.654323v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2508/12132325/6d0d80decca7/nihpp-2025.05.15.654323v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2508/12132325/9944935c1afb/nihpp-2025.05.15.654323v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2508/12132325/0840b2f61424/nihpp-2025.05.15.654323v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2508/12132325/9a21c955d5e1/nihpp-2025.05.15.654323v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2508/12132325/baa60c02a7c5/nihpp-2025.05.15.654323v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2508/12132325/6d0d80decca7/nihpp-2025.05.15.654323v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2508/12132325/9944935c1afb/nihpp-2025.05.15.654323v1-f0005.jpg

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本文引用的文献

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A nociceptive amygdala-striatal pathway modulating affective-motivational pain.一条调节情感动机性疼痛的伤害性杏仁核-纹状体通路。
Sci Adv. 2025 Jul 25;11(30):eado2837. doi: 10.1126/sciadv.ado2837. Epub 2025 Jul 23.
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Striatal dopamine represents valence on dynamic regional scales.纹状体多巴胺在动态区域尺度上代表效价。
J Neurosci. 2025 Mar 17;45(17). doi: 10.1523/JNEUROSCI.1551-24.2025.
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Input-output organization of the mouse BLA-projecting IL neurons.投射至小鼠基底外侧杏仁核的终纹床核神经元的输入-输出组织
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Valence and salience encoding in the central amygdala.中央杏仁核中的效价和显著性编码。
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How Dopamine Enables Learning from Aversion.多巴胺如何使人从厌恶中学习。
Curr Opin Behav Sci. 2025 Feb;61. doi: 10.1016/j.cobeha.2024.101476. Epub 2024 Dec 21.
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Dopamine release and dopamine-related gene expression in the amygdala are modulated by the gastrin-releasing peptide in opposite directions during stress-enhanced fear learning and extinction.在应激增强的恐惧学习和消退过程中,胃泌素释放肽以相反的方向调节杏仁核中的多巴胺释放和多巴胺相关基因表达。
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Orbitofrontal Cortex Mediates Sustained Basolateral Amygdala Encoding of Cued Reward-Seeking States.眶额皮层介导线索奖励寻求状态的持续基底外侧杏仁核编码。
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