Ventromedial hypothalamus (VMHvl) nNOS neurons regulate social behaviors in a sex-specific manner

Neuronal nitric oxide synthase (nNOS) neurons are ubiquitously spread in the mouse brain. Data using knockouts and pharmacology have revealed that nNOS is essential for the display of sexual and aggressive behavior. Yet, the specific neuronal populations regulating those behaviors remain elusive. Here, we aim to study the role of the ventromedial hypothalamus (VMHvl)-nNOS neurons in social behaviors in both sexes. First, we evaluate whether the expression of nNOS overlaps with the well characterized estrogen receptor alpha (ERα + )-VMHvl population. Next, we assess how different social stimuli affected VMHvl-nNOS neurons’ activity. Lastly, we use transgenic mice and viral approaches to ablate VMHvl-nNOS neurons and evaluate their impact on behavior. Our findings suggest that nNOS neurons constitute a small cluster within the VMHvl-ERα+ population that regulates social behaviors in a sex-specific manner. In males, those neurons seem to be essential for aggression, whereas in females for sexual behavior and social motivation.