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<p>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<sup>+</sup>) 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<sup>+</sup> 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.</p>

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Oxytocin facilitates social behavior of female rats via selective modulation of interneurons in the medial prefrontal cortex

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月20日

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  • Stephanie Schimmer,
  • Alan Kania,
  • Arthur 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 Boender,
  • Yuval Podpecan,
  • Franziska Schommer,
  • Tim Schubert,
  • Anna Sanetra,
  • Aleksandra Trenk,
  • Anna Gugula,
  • René Hurlemann,
  • Shlomo Wagner,
  • Yulong Li,
  • Ferdinand Althammer,
  • Anna Blasiak,
  • Sarah Melzer,
  • Hannah Monyer,
  • Alexandre Charlet,
  • Marina Eliava,
  • Valery Grinevich

摘要

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.