REGULATION OF SEXUAL BEHAVIOUR BY THE OXYTOCIN-RECEPTOR EXPRESSING NEURONS IN THE LATERAL SEPTUM

The lateral septum (LS) is a key brain region involved in the regulation of social and sexual behaviours which is essential for species survival. Within this region, oxytocin receptor–expressing (OxtR) neurons have emerged as an important substrate for reproductive behaviour. Although the acute involvement of LS OxtR neurons in social aspects of sexual activity -such as social fear aversion-has been previously reported (Grossmann et al., 2024), their long-term role in integrating sexual and social processes remains poorly understood.
In the present study, we investigated the contribution of LS OxtR neurons to male sexual behaviour using a chemogenetic approach in mice. OxtR-expressing neurons in the LS were selectively inhibited through viral-mediated expression of inhibitory DREADDs, followed by clozapine-N-oxide (CNO) administration. Behavioral assays assessed male mice’s interactions with same- and opposite-sex conspecifics before and after sexual experience.
Our results demonstrate that LS OxtR neurons flexibly gate male preference for female vs male conspecifics depending on sexual experience–dependent manner. In sexually naive control males, approach behaviour toward females was reduced compared with sexually experienced control males, consistent with social avoidance. Notably, this avoidance was abolished when LS OxtR neurons were inhibited in sexually naive mice.
Together, these findings provide new insights into the neural circuitry underlying male sexual behavior and highlight a critical role of oxytocin signaling in the LS in shaping experience-dependent sexual and social interactions.
We gratefully acknowledge support by DFG Walter Benjamin Programme to D.K. (project number: 551841466) and DFG SFB1089 and EXC2030-CECAD to T.K.