Astrocytes control oxytocin-based maternal behavior via connexin 30

ABSTRACT Prosocial and affiliative behaviors rely on complex neuroendocrine neuronal circuits. Dynamic neuroglial interactions play prominent roles in shaping synaptic networks, whose alterations contribute to psychiatric disorders associated with social deficits. However, a role for astrocytes in regulating maternal behavior remains elusive. Here we show that female mice exhibiting increased oxytocin levels in the hypothalamic supraoptic nucleus upon social interactions with pups display neuroglial structural plasticity and downregulation of astroglial connexin 30, a protein involved in morphological remodeling. We found that impairing astroglial connexin 30 expression alters the structural properties of astrocytes by decreasing their volume and coverage of oxytocinergic synapses in the supraoptic nucleus of female mice. This functionally sets levels of plasma oxytocin and maternal behavior, exacerbating maternal care in virgin pup-naïve female mice deficient for astroglial Cx30. Hypothalamic astrocytes, via connexin 30, are thus key determinants of oxytocin-based maternal behavior, whose alteration is known to impair social skills development in offspring.