Stephanie Schimmer, Alan Kania, A. Lefevre, Konstantinos Afordakos, Kai-Yi Wang, Julia Lebedeva, Andrei Rozov, Androniki Raftogianni, Rishika Tiwari, Shai Netser, Ana Zovko, Huma Shaheen, Jonas Schimmer, Ryan Patwell, Clémence Denis, Valentin Grelot, Hugues Petitjean, Lan Geng, Dimitri Hefter, Arjen J. Boender, Yuval Podpecan, Franziska Schommer, Tim Schubert, Anna Magdalena Sanetra, Aleksandra Trenk, Anna Guguła, R. Hurlemann, Shlomo Wagner, Y. Li, Ferdinand Althammer, Anna Blasiak, Sarah Maria Melzer, Hannah Monyer, Alexandre Charlet, Marina Eliava, Valery Grinevich
Abstract The hypothalamic neuropeptide oxytocin is best known for its prosocial behavioral effects. However, the precise anatomical and cellular targets for oxytocin in the cortex during social behavior remain elusive. Here we show that oxytocin neurons project directly to the medial prefrontal cortex where evoked axonal oxytocin release facilitates social behaviors in adult female rats. In conjunction, we report that local oxytocin receptor-expressing (OTR + ) cells are predominantly interneurons, whose activation promotes social interaction. Notably, this prosocial effect persists even under physiological challenge (hunger), pointing to a dedicated prosocial circuit capable of overriding primary survival drives. We further demonstrate that activation of these OTR + interneurons inhibits principal cells specifically projecting to the basolateral amygdala, thus providing a putative mechanism of selective oxytocin action in this sociability-promoting cortical network.