A neuroglial circuit for maternal behavior

Prosocial and affiliative behaviors depend on intricate neuroendocrine neuronal circuits. Dynamic neuroglial interactions play pivotal roles in shaping synaptic networks, whose alterations are known to contribute to psychiatric disorders linked to social deficits. Yet the involvement of astrocytes in regulating maternal behavior remains unclear. In this study, we used a pup sensitization model with virgin pup naïve female adult mice, to investigate the molecular mechanisms underlying maternal behavior in the supraoptic nucleus. We assessed oxytocin-level in the extracellular fluid through in vivo microdialysis, and in the plasma using radioimmunoassay. We studied changes in astrocytic structural properties by combining quantitative immunohistochemistry, electron microscopy and stimulated emission depletion super resolution microscopy. We tested the maternal behavior by employing three different behavioral tests: direct interaction, pup retrieval, nest building. Pharmacological and genetic modifications were used to identify targets. Our results show that female mice exhibit elevated oxytocin levels and structural plasticity through social interactions with pups. The changes were associated with downregulation of an astroglial protein in the supraoptic nucleus involved in morphological remodeling. Disrupting this protein results in structural changes in astrocytes, altering their volume and coverage of oxytocinergic synapses, which regulates oxytocin levels and maternal behavior. Our findings highlight the critical role of supraoptic nucleus astrocytes in influencing oxytocin-based maternal behavior - a factor known to impair social skills development in offspring.