Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nature. 2020 Apr;580(7802):239-244. doi: 10.1038/s41586-020-2158-3. Epub 2020 Apr 1.
The neurotransmitter dopamine is required for the reinforcement of actions by rewarding stimuli. Neuroscientists have tried to define the functions of dopamine in concise conceptual terms, 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 studied, the effects of dopamine on larger-scale neural activity profiles are less well-understood. Here we combine dynamic dopamine-sensitive molecular imaging 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.
神经递质多巴胺对于奖赏刺激所增强的行为至关重要。神经科学家试图用简洁的概念术语来定义多巴胺的功能，但多巴胺释放的实际影响取决于其在大脑中的广泛影响。尽管多巴胺能信号传递的分子和细胞效应已被广泛研究，但多巴胺对更大规模的神经活动谱的影响却知之甚少。在这里，我们结合动态多巴胺敏感分子成像和功能磁共振成像，以确定纹状体多巴胺释放如何塑造大鼠大脑对奖赏刺激的局部和全局反应。我们发现，多巴胺通过可量化的跨亚区变化的突触后效应，一致地改变了纹状体大部分区域的刺激反应持续时间，但不改变其幅度。纹状体多巴胺释放还增强了一个远程反应网络，我们使用依赖神经化学的功能连接分析来描绘该网络。多巴胺驱动的热点显著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，其作用范围远远超出其峰值释放部位，并导致与动机行为相关的远程神经群体的激活增强。我们的发现还为多巴胺能功能的脑区生物标志物提供了依据，并为改善与学习和成瘾相关的神经影像学结果的解释提供了基础。
