Remote memories depend on coordinated activity in the hippocampus and frontal cortices, but the timeline of these interactions is debated. Astrocytes sense and modify neuronal activity, but their role in remote memory is scarcely explored. We expressed the G_i-coupled designer receptor hM4Di in CA1 astrocytes and discovered that astrocytic manipulation during learning specifically impaired remote, but not recent, memory recall and decreased activity in the anterior cingulate cortex (ACC) during retrieval. We revealed massive recruitment of ACC-projecting CA1 neurons during memory acquisition, which was accompanied by the activation of ACC neurons. Astrocytic G_i activation disrupted CA3 to CA1 communication in vivo and reduced the downstream response in the ACC. In behaving mice, it induced a projection-specific inhibition of CA1-to-ACC neurons during learning, which consequently prevented ACC recruitment. Finally, direct inhibition of CA1-to-ACC-projecting neurons spared recent and impaired remote memory. Our findings suggest that remote memory acquisition involves projection-specific functions of astrocytes in regulating CA1-to-ACC neuronal communication.

远程记忆依赖于海马和额叶皮层的协调活动，但这些相互作用的时间线存在争议。星形胶质细胞感知和修改神经元活动，但很少探索它们在远程记忆中的作用。我们在 CA1 星形胶质细胞中表达了 G _i偶联设计受体 hM4Di，并发现学习期间的星形胶质细胞操作会特别损害远程但不是近期的记忆回忆，并在检索期间前扣带皮层 (ACC) 的活动减少。我们揭示了在记忆获取过程中大量募集 ACC 投射的 CA1 神经元，这伴随着 ACC 神经元的激活。星形胶质_细胞激活破坏了体内 CA3 与 CA1 的通讯，并减少了 ACC 中的下游反应。在行为小鼠中，它在学习过程中诱导 CA1 到 ACC 神经元的投射特异性抑制，从而阻止了 ACC 的募集。最后，直接抑制 CA1 到 ACC 投射的神经元可以避免近期和受损的远程记忆。我们的研究结果表明，远程记忆获取涉及星形胶质细胞在调节 CA1 到 ACC 神经元通讯中的投射特异性功能。