You know I need you for the oxytocin

The world is undergoing an epidemic of loneliness and isolation, underscoring the importance and urgency for understanding the neural mechanisms of social interactions. While there is a growing amount of evidence showing the relevance of oxytocin for social behaviors, less is known about how social interactions – or the lack of them – affect oxytocin neurons. Our work shows a sex-specific effect of long-term social deprivation, decreasing oxytocin levels and delaying affiliation upon reunion in male mice. This phenotype was rescued by chemogenetic stimulation of the endogenous oxytocin system and by delivery of exogenous oxytocin during the isolation period. Moreover, both approaches induced an upregulation of endogenous oxytocin expression, a phenomenon that we named “the local oxytocin positive feedback loop”. We found that this loop is dependent on neuron-glia communication, in which astrocytes can sense and modulate the oxytocin system. This mechanism is relevant for social interactions and represents a potential therapeutic target for disorders and diseases involving social dysfunction – such as autism spectrum disorder and Alzheimer’s disease.