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Local and global consequences of reward-evoked striatal dopamine release
Nature ( IF 64.8 ) Pub Date : 2020-04-01 , DOI: 10.1038/s41586-020-2158-3
Nan Li 1 , Alan Jasanoff 1, 2, 3
Affiliation  

The neurotransmitter dopamine is required for the reinforcement of actions by rewarding stimuli1. Neuroscientists have tried to define the functions of dopamine in concise conceptual terms2, but the practical implications of dopamine release depend on its diverse brain-wide consequences. Although molecular and cellular effects of dopaminergic signalling have been extensively studied3, the effects of dopamine on larger-scale neural activity profiles are less well-understood. Here we combine dynamic dopamine-sensitive molecular imaging4 and functional magnetic resonance imaging to determine how striatal dopamine release shapes local and global responses to rewarding stimulation in rat brains. We find that dopamine consistently alters the duration, but not the magnitude, of stimulus responses across much of the striatum, via quantifiable postsynaptic effects that vary across subregions. Striatal dopamine release also potentiates a network of distal responses, which we delineate using neurochemically dependent functional connectivity analyses. Hot spots of dopaminergic drive notably include cortical regions that are associated with both limbic and motor function. Our results reveal distinct neuromodulatory actions of striatal dopamine that extend well beyond its sites of peak release, and that result in enhanced activation of remote neural populations necessary for the performance of motivated actions. Our findings also suggest brain-wide biomarkers of dopaminergic function and could provide a basis for the improved interpretation of neuroimaging results that are relevant to learning and addiction.



中文翻译:

奖励诱发纹状体多巴胺释放的局部和全球后果

神经递质多巴胺是通过奖励刺激1强化行动所必需的。神经科学家试图用简洁的概念术语来定义多巴胺的功能2,但多巴胺释放的实际意义取决于其在大脑范围内的各种后果。尽管多巴胺能信号传导的分子和细胞效应已被广泛研究3,但多巴胺对大规模神经活动谱的影响却鲜为人知。在这里,我们结合动态多巴胺敏感分子成像4和功能性磁共振成像,以确定纹状体多巴胺的释放如何影响大鼠大脑对奖励刺激的局部和全局反应。我们发现,多巴胺通过不同子区域的可量化突触后效应持续改变大部分纹状体刺激反应的持续时间,但不改变幅度。纹状体多巴胺释放也增强了远端反应网络,我们使用神经化学依赖性功能连接分析来描述。多巴胺能驱动的热点尤其包括与边缘和运动功能相关的皮质区域。我们的研究结果揭示了纹状体多巴胺的独特神经调节作用,远远超出其峰值释放部位,并导致增强执行动机动作所必需的远程神经群的激活。我们的研究结果还表明了多巴胺能功能的全脑生物标志物,并且可以为改进与学习和成瘾相关的神经影像学结果的解释提供基础。

更新日期:2020-04-01
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