Social Behaviour Shapes Hypothalamic Neural Ensemble Representations Of Conspecific Sex

All animals possess a repertoire of innate (or instinctive(1,2)) behaviors, which can be performed without training. Whether such behaviors are mediated by anatomically distinct and/or genetically specified neural pathways remains a matter of debate(3-5). Here we report that hypothalamic neural ensemble representations underlying innate social behaviors are shaped by social experience. Estrogen receptor 1-expressing (Esr1(+)) neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl) control mating and fighting in rodents(6-8). We used microendoscopy(9) to image VMHvl Esr1(+) neuronal activity in male mice engaged in these social behaviours. In sexually and socially experienced adult males, divergent and characteristic neural ensembles represented male vs. female conspecifics. But surprisingly, in inexperienced adult males, male and female intruders activated overlapping neuronal populations. Sex-specific ensembles gradually separated as the mice acquired social and sexual experience. In mice permitted to investigate but not mount or attack conspecifics, ensemble divergence did not occur. However, 30 min of sexual experience with a female was sufficient to promote both male vs. female ensemble separation and attack, measured 24 hr later. These observations uncover an unexpected social experience-dependent component to the formation of hypothalamic neural assemblies controlling innate social behaviors. More generally, they reveal plasticity and dynamic coding in an evolutionarily ancient deep subcortical structure that is traditionally viewed as a “hard-wired” system.