Abstract

Abstract The neuropeptide oxytocin (OXT) is well recognized for eliciting anxiolytic effects and promoting social reward. However, there is emerging evidence to show that OXT increases aversive events. These seemingly inconsistent results may be attributable to the broad OXT receptor (OXTr) expression in the central nervous system. We applied chemo/optogenetic approach to selectively stimulate septal neurons expressing OXT and /or OXTr. We found that activation of septal OXT or OXTr neurons induced anxiety- but not depressive-like behavior. Septal OXTr neurons projected dense fibers to the diagonal band’s horizontal limb (HDB), and selective stimulation of those HDB projections also elicited anxiety-like behavior. 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 novel wireless photometry results show that ventral hippocampal neurons and septal OXT or PXTR neurons are stimulated under anxiety conditions. More interestingly, selective optogenetic stimulation of ventral hippocampus or their projections to the septum inhibited the neurons localized within the HDB. Our data collectively reveal that septal OXTr neurons increase anxiety by projecting inhibitory GABAergic inputs to the HDB, and probably partake in the ventral hippocampus-dependent anxiety. Keywords: Chemo/Optogenetic, Electrophysiology, Photometry, Anxiety

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