SUPPRESSION OF AGGRESSION BY AN OXYTOCIN RECEPTOR POSITIVE MPOA–VMH PATHWAY

The medial preoptic area (MPOA) is a key center for hormonal and social integration, yet its precise role in aggression is less clear. Previously, we found that the posterior intralaminar thalamic nucleus (PIL), particularly neurons containing parathyroid hormone 2 (PTH2), projects to the MPOA to enhance prosocial behaviour and mitigate aggression. This study examines the role of oxytocin receptor (OTR) expressing neurons in the MPOA.
Anatomical tracing revealed that MPOA OTR neurons project to key regions, including the ventromedial hypothalamic nucleus (VMH) and the medial amygdala (MeA). Double immunolabeling revealed the presence of PTH2 fiber terminals from the PIL in proximity to these MPOA OTR neurons.
Using OTR-Cre transgenic male rats and chemogenetic manipulation (DREADD), we conducted evaluations of social behaviour through the resident-intruder test. Inhibition of MPOA OTR neurons led to a significant increase in aggression and a decrease in positive valence behaviours. Conversely, stimulation of these neurons promoted prosocial actions without altering aggression levels, likely due to the naturally low baseline aggression in the subjects.
Furthermore, inhibiting MPOA OTR neurons during social interactions resulted in a significant increase in c-Fos expression in the VMH. Notably, targeted chemogenetic activation of the specific MPOA OTR-VMH pathway led to increased aggression and decreased prosocial behaviours.
In conclusion, OTR-positive MPOA neurons likely act as a central hub suppressing aggression by inhibiting the VMH and increasing prosocial behaviours. PTH2-containing PIL neurons may target this population, conveying somatosensory information, highlighting the OTR-positive neurons as a key relay integrating PIL inputs and influencing social behaviour.