Dopamine controls essential brain functions through volume transmission. Different from fast synaptic transmission, where neurotransmitter release and receptor activation are tightly coupled by an active zone, dopamine transmission is widespread and may not necessitate these organized release sites. Here, we determine whether striatal dopamine secretion employs specialized machinery for release. Using super resolution microscopy, we identified co-clustering of the active zone scaffolding proteins bassoon, RIM and ELKS in ∼30% of dopamine varicosities. Conditional RIM knockout disrupted this scaffold and, unexpectedly, abolished dopamine release, while ELKS knockout had no effect. Optogenetic experiments revealed that dopamine release was fast and had a high release probability, indicating the presence of protein scaffolds for coupling Ca²⁺ influx to vesicle fusion. Hence, dopamine secretion is mediated by sparse, mechanistically specialized active zone-like release sites. This architecture supports spatially and temporally precise coding for dopamine and provides molecular machinery for regulation.

中文翻译：

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多巴胺分泌是由稀疏的活性区样释放位点介导的。

多巴胺通过体积传输来控制基本的大脑功能。与快速的突触传递不同，神经递质的释放和受体的激活通过活动区紧密耦合，而多巴胺的传播却很普遍，可能不需要这些有组织的释放位点。在这里，我们确定纹状体多巴胺分泌是否采用专门的机制进行释放。使用超高分辨率显微镜，我们确定了约30％的多巴胺静脉曲张中活动区支架蛋白巴松，RIM和ELKS的共簇。有条件的RIM敲除破坏了该支架，并且出乎意料地取消了多巴胺的释放，而ELKS敲除则没有效果。光遗传学实验表明，多巴胺释放快且具有高释放概率，表明存在耦合钙的蛋白质支架。²⁺流入囊泡融合。因此，多巴胺的分泌是由稀疏的，机械特化的活性区样释放位点介导的。该体系结构支持对多巴胺的时空精确编码，并提供调节分子的机制。