Early life adversity impairs visually evoked innate defensive behaviors via oxytocin signaling

Recent studies have shown that ELA disrupts conditional fear behavior in mice; however, whether ELA affects innate fear behavior remains largely unknown. Here, we report that ELA induced by social deprivation on postnatal days 10-20 impairs looming-evoked innate defensive behaviors via an oxytocin (OT) signaling deficit. ELA leads to decreased OT receptor mRNA levels in the intermediate and deep layers of the superior colliculus (IDSC), and knockdown of this receptor in the superior colliculus mimics the defensive behavior deficit induced by ELA. OT neurons in the paraventricular nucleus of the hypothalamus modulate looming-evoked innate defensive behavior through projections to the IDSC. Moreover, intranasal OT ameliorated ELA-induced deficits in defensive behavior. This study provides a theoretical basis for understanding how ELA induces a fear processing deficit that contributes to psychopathological outcomes and represents an initial step toward identifying potential treatment strategies.