Dopamine is required for working memory, but how it modulates the large-scale cortex is unknown. Here, we report that dopamine receptor density per neuron, measured by autoradiography, displays a macroscopic gradient along the macaque cortical hierarchy. This gradient is incorporated in a connectome-based large-scale cortex model endowed with multiple neuron types. The model captures an inverted U-shaped dependence of working memory on dopamine and spatial patterns of persistent activity observed in over 90 experimental studies. Moreover, we show that dopamine is crucial for filtering out irrelevant stimuli by enhancing inhibition from dendrite-targeting interneurons. Our model revealed that an activity-silent memory trace can be realized by facilitation of inter-areal connections and that adjusting cortical dopamine induces a switch from this internal memory state to distributed persistent activity. Our work represents a cross-level understanding from molecules and cell types to recurrent circuit dynamics underlying a core cognitive function distributed across the primate cortex.

工作记忆需要多巴胺，但它如何调节大面积皮层尚不清楚。在这里，我们报告了通过放射自显影测量的每个神经元的多巴胺受体密度，沿着猕猴皮层层次显示出宏观梯度。这种梯度被整合到一个基于连接组的大规模皮层模型中，该模型具有多种神经元类型。该模型捕获了工作记忆对多巴胺的倒 U 形依赖性，以及在 90 多项实验研究中观察到的持续活动的空间模式。此外，我们表明多巴胺通过增强针对树突的中间神经元的抑制作用，对于过滤掉无关刺激至关重要。我们的模型表明，可以通过促进区域间连接来实现活动无声的记忆轨迹，并且调节皮质多巴胺会诱导从这种内部记忆状态到分布式持续活动的转换。我们的工作代表了从分子和细胞类型到分布在灵长类动物皮层的核心认知功能的循环回路动力学的跨层次理解。