Chronic stress could induce severe cognitive impairments. Despite extensive investigations in mammalian models, the underlying mechanisms remain obscure. Here, we show that chronic stress could induce dramatic learning and memory deficits in Drosophila melanogaster. The chronic stress–induced learning deficit (CSLD) is long lasting and associated with other depression-like behaviors. We demonstrated that excessive dopaminergic activity provokes susceptibility to CSLD. Remarkably, a pair of PPL1-γ1pedc dopaminergic neurons that project to the mushroom body (MB) γ1pedc compartment play a key role in regulating susceptibility to CSLD so that stress-induced PPL1-γ1pedc hyperactivity facilitates the development of CSLD. Consistently, the mushroom body output neurons (MBON) of the γ1pedc compartment, MBON-γ1pedc>α/β neurons, are important for modulating susceptibility to CSLD. Imaging studies showed that dopaminergic activity is necessary to provoke the development of chronic stress–induced maladaptations in the MB network. Together, our data support that PPL1-γ1pedc mediates chronic stress signals to drive allostatic maladaptations in the MB network that lead to CSLD.

慢性压力会导致严重的认知障碍。尽管对哺乳动物模型进行了广泛的研究，但潜在的机制仍然不清楚。在这里，我们表明，慢性压力会导致黑腹果蝇出现剧烈的学习和记忆障碍。. 慢性压力诱发的学习缺陷 (CSLD) 持续时间长，并与其他类似抑郁的行为有关。我们证明了过度的多巴胺能活动会引起对 CSLD 的易感性。值得注意的是，一对投射到蘑菇体 (MB) γ1pedc 隔室的 PPL1-γ1pedc 多巴胺能神经元在调节对 CSLD 的易感性中起关键作用，因此应激诱导的 PPL1-γ1pedc 过度活跃促进了 CSLD 的发展。一致地，γ1pedc室的蘑菇体输出神经元（MBON），MBON-γ1pedc>α/β神经元，对于调节对CSLD的易感性很重要。影像学研究表明，多巴胺能活性对于激发 MB 网络中慢性压力诱导的适应不良的发展是必要的。一起，