Aversive memories are important for survival, and dopaminergic signaling in the hippocampus has been implicated in aversive learning. However, the source and mode of action of hippocampal dopamine remain controversial. Here, we utilize anterograde and retrograde viral tracing methods to label midbrain dopaminergic projections to the dorsal hippocampus. We identify a population of midbrain dopaminergic neurons near the border of the substantia nigra pars compacta and the lateral ventral tegmental area that sends direct projections to the dorsal hippocampus. Using optogenetic manipulations and mutant mice to control dopamine transmission in the hippocampus, we show that midbrain dopamine potently modulates aversive memory formation during encoding of contextual fear. Moreover, we demonstrate that dopaminergic transmission in the dorsal CA1 is required for the acquisition of contextual fear memories, and that this acquisition is sustained in the absence of catecholamine release from noradrenergic terminals. Our findings identify a cluster of midbrain dopamine neurons that innervate the hippocampus and show that the midbrain dopamine neuromodulation in the dorsal hippocampus is sufficient to maintain aversive memory formation.

厌恶性记忆对生存很重要，海马中的多巴胺能信号传导与厌恶性学习有关。然而，海马多巴胺的来源和作用方式仍存在争议。在这里，我们利用顺行和逆行病毒追踪方法来标记背侧海马的中脑多巴胺能投射。我们在黑质致密部和向背侧海马体发送直接投射的外侧腹侧被盖区域附近识别出一群中脑多巴胺能神经元。使用光遗传学操作和突变小鼠来控制海马中的多巴胺传递，我们表明中脑多巴胺在编码情境恐惧期间有效地调节厌恶记忆的形成。而且，我们证明背侧 CA1 中的多巴胺能传递是获得情境恐惧记忆所必需的，并且这种获得是在没有去甲肾上腺素能末端释放儿茶酚胺的情况下持续的。我们的研究结果确定了一组支配海马的中脑多巴胺神经元，并表明背侧海马中的中脑多巴胺神经调节足以维持厌恶记忆的形成。