MEDIAL PREOPTIC OXYTOCIN RECEPTOR-POSITIVE NEURONS CONTROL SOCIAL BEHAVIOR IN RATS

Oxytocin is released in the brain in response to social interactions and acts via the oxytocin receptor (OTR) to regulate social behavior in rodents. The medial preoptic area (MPOA) contains a dense population of OTR-expressing neurons and serves as a key hub for social behavioral control. While the MPOA is linked to reproductive behaviors, increasing evidence suggests its role in affiliative social behavior and social homeostasis.
We investigated the functional contribution of MPOA OTR-expressing neurons to interfemale social behavior using chemogenetic manipulation. Female OTR-Cre Sprague–Dawley rats received Cre-dependent excitatory or inhibitory DREADD constructs targeted to the MPOA via adeno-associated viral vectors. Behavioral effects following DREADD activation were compared to vehicle-treated control days.
Chemogenetic activation of MPOA OTR+ neurons significantly increased the frequency and duration of affiliative social behaviors, including allogrooming, body sniffing, mounting, and following, while reducing moving-away and non-social behaviors. In contrast, chemogenetic inhibition of MPOA OTR+ neurons resulted in a significantly decrease in the duration and frequency of body sniffing and following behaviors and increased passive social interactions.
Fiber photometry revealed increased neuronal activity during anogenital sniffing, which we identified as the initiating element of a behavioral sequence promoting direct social interactions. Finally, anatomical tracing demonstrated projections from MPOA OTR+ neurons to multiple regions implicated in social behavior, with particularly dense innervation of the lateral septum. Together, these findings demonstrate that MPOA OTR-expressing neurons bidirectionally control key components of social interactions between adult female conspecifics.
Grants: EKÖP-25-2-40, NAP2022-I-3/2022, NKFIH OTKA K146077 and NKKP OTKA Excellence 151425.