Activation of septal OXTr neurons induces anxiety- but not depressive-like behaviors

The neuropeptide oxytocin (OXT) is well recognized for eliciting anxiolytic effects and promoting social reward. However, emerging evidence shows that OXT increases aversive events. These seemingly inconsistent results may be attributable to the broad OXT receptor (OXTr) expression in the central nervous system. This study selectively activated septal neurons expressing OXTr using chemogenetics. We found that chemogenetic activation of septal OXTr neurons induced anxiety- but not depressive-like behavior. In addition, septal OXTr neurons projected dense fibers to the horizontal diagonal band of Broca (HDB), and selective stimulation of those HDB projections also elicited anxiety-like behaviors. We also found that septal OXTr neurons express the vesicular GABA transporter (vGAT) protein and optogenetic stimulation of septal OXTr projections to the HDB inactivated HDB neurons. Our data collectively reveal that septal OXTr neurons increase anxiety by projecting inhibitory GABAergic inputs to the HDB.