A NEUROGLIAL CIRCUIT FOR MATERNAL BEHAVIOR

Prosocial and affiliative behaviors rely on finely tuned neuroendocrine circuits. Within these circuits, dynamic neuron–glia interactions shape synaptic architecture, and their disruption contributes to psychiatric disorders marked by social deficits. However, whether and how astrocytes regulate maternal behavior remains poorly understood.

Here, we used a pup-sensitization paradigm in virgin, pup-naïve adult female mice to dissect the molecular mechanisms supporting maternal behavior within the supraoptic nucleus (SON), comparing wild-type animals to connexin 30–deficient mice. Oxytocin release was quantified in the extracellular space using in vivo microdialysis and in plasma by radioimmunoassay. Astrocytic structural adaptations were characterized through a multimodal approach combining quantitative immunohistochemistry, electron microscopy, and stimulated emission depletion (STED) super-resolution microscopy. Maternal behavior was assessed using three complementary assays (direct pup interaction, pup retrieval, and nest building), and pharmacological and genetic interventions were leveraged to identify the underlying cellular targets.

We show that social interactions with pups induce a robust increase in oxytocin levels alongside pronounced structural plasticity in the SON. These changes coincide with the downregulation of an astroglial protein implicated in morphological remodeling. Disrupting this protein drives astrocytic structural alterations, modifying astrocyte volume and their ensheathment of oxytocinergic synapses, thereby tuning extracellular oxytocin levels and shaping maternal responses.

Together, these findings identify SON astrocytes as key regulators of oxytocin-dependent maternal behavior, with potential implications for offspring social development, an outcome known to be vulnerable when early-life caregiving is altered.