Astrocytes are an indispensable part of signal processing within the mammalian brain. Thus, the mode of action of a neuropeptide such as oxytocin (OXT) can only be fully understood considering this integral part of the CNS. Here, we show that OXT regulates astrocytic gene expression, intracellular signaling and specific proteins both in vitro and in vivo. This translates into rapid regulation of astroglial structural and functional properties including cytoskeletal plasticity, coverage of synapses and gap-junction coupling. At the molecular level, we identify the previously undescribed Sp1-Gem signaling cascade as the key driver for these cell type-specific OXT effects. Finally at the behavioral level, we found in vivo that OXT requires astrocytes to exert its well described anxiolytic properties within the hypothalamic paraventricular nucleus. Thus, our study points to OXT receptor-expressing astrocytes as a critical component of the brain OXT system.

星形胶质细胞是哺乳动物大脑内信号处理不可或缺的一部分。因此，只有考虑到 CNS 的这一组成部分，才能完全理解催产素 （OXT） 等神经肽的作用方式。在这里，我们表明 OXT 在体外和体内调节星形胶质细胞基因表达、细胞内信号传导和特异性蛋白。这转化为星形胶质细胞结构和功能特性的快速调节，包括细胞骨架可塑性、突触覆盖和间隙连接耦合。在分子水平上，我们确定以前未描述的 Sp1-Gem 信号级联是这些细胞类型特异性 OXT 效应的关键驱动因素。最后，在行为层面，我们在体内发现 OXT 需要星形胶质细胞在下丘脑室旁核内发挥其明确描述的抗焦虑特性。因此，我们的研究指出，表达 OXT 受体的星形胶质细胞是大脑 OXT 系统的关键组成部分。