Astrocytes mediate a positive feedback loop for oxytocin

Abstract Social interactions are critical for well-being and survival. Oxytocin neurons in the paraventricular nucleus of the hypothalamus help regulate social behaviors in many species, and respond to social stimuli to promote pro-social interactions. Here, we show that chronic social isolation reduced production of oxytocin peptide, and led to a delay in the onset of huddling behavior upon resocialization in male mice. Exogenous oxytocin treatment prevented both the behavioral and molecular effects of social deprivation. Using conditional knockouts, we found that oxytocin-induced oxytocin expression was mediated by local hypothalamic astrocytes. Oxytocin signaling in astrocytes upregulated the expression of a retinoic acid-synthesizing enzyme Aldh1a1, and retinoic acid increased oxytocin expression. These findings reveal a mechanism in which astrocytes can sense and control neuropeptide levels to influence social behaviors. Competing Interest Statement S.A.L. maintains a financial interest in AstronauTx and Synapticure. S.A.L. is on the Scientific Advisory Board of the Global BioAccess Fund.