A Brain-Wide Atlas of Astrocytic Oxytocin Receptors Reveals a Glial Basis for Nucleus Accumbens Modulation of Affiliative Behavior.

Until recently, it was widely assumed that oxytocin signaling occurred exclusively through the activation of neuronal oxytocin receptors, with neurons being the primary targets of released oxytocin. However, this view was challenged by the discovery of functional oxytocin receptors in central amygdala astrocytes, which are essential for the proper function of local neuronal microcircuits. Since then, astrocytic oxytocin receptors have been implicated in various aspects of rodent physiology and behavior, yet it remains unclear whether this mechanism is region-specific or widespread across the brain. Here, we provide extensive anatomical data on oxytocin receptor expression in mice and rats, functionally validated through calcium imaging. Based on this mapping and using genetic, calcium imaging and behavioral approaches, we further demonstrate a critical role for oxytocin receptor-expressing astrocytes in the nucleus accumbens in social behavior. In summary, our findings demonstrate that oxytocin receptors are widely expressed in astrocytes across different brain regions. In the nucleus accumbens, these receptors modulate social behavior-an observation with significant implications for the current model of oxytocinergic modulation in the brain.