THE ROLE OF CORTICO-PREOPTIC PROJECTIONS FROM THE MEDIAL PREFRONTAL CORTEX IN THE CONTROL OF SOCIAL BEHAVIOUR IN RATS

The medial prefrontal cortex (mPFC) influences social behaviour through distinct populations of projection neurons. In this study, we determined the projection pattern of mPFC neurons targeting the medial preoptic area (MPOA) and investigated the functional role of this pathway in social behaviour using chemogenetic approaches.
Stimulatory and inhibitory designer receptors were selectively expressed in MPOA-projecting mPFC neurons. Labelled collaterals were observed in the MPOA and in several subcortical regions, including the accumbens nucleus, ventral pallidum, lateral septum, paraventricular and ventromedial hypothalamic nuclei.
Chemogenetic activation of cortico-preoptic mPFC neurons reduced sociability in the three chamber test, although direct social interactions were not affected. Inhibition of MPOA-projecting mPFC neurons increased the duration of anogenital sniffing and mounting behavioural elements during direct social interactions but did not alter sociability in the three-chamber test. In another experiment, we selectively activated the mPFC→MPOA pathway by administering CNO into the MPOA after AAV delivery to the mPFC. This manipulation reduced chasing behaviour. In turn, local inhibition increased chasing and mounting behaviours. Sociability remained unaffected by both stimulation and inhibition of the pathway.
The findings indicate that mPFC neurons projecting to the MPOA contribute to the regulation of social behaviour. The differences in the effects of manipulating the cortico-preoptic neurons with the two approaches suggest distinct roles of the subcortical mPFC projections in social behavioural regulation.
Grant support: EKÖP-25 University Excellence Scholarship Program of the Ministry for Culture and Innovation, Richter Gedeon Centenary Foundation Talentum Scholarship 2025, NAP3 (NAP2022-I-3/2022), NKFIH OTKA K146077, NKP Excellence 151425.