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

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 (OTR ⁺ ) expressing cells are predominantly interneurons whose activation promotes social interaction. In particular, in a state of food deprivation, this inhibitory neuronal subpopulation shifts the preference from appetitive food stimuli towards a social stimulus. 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.