Social behaviour shapes hypothalamic neural ensemble representations of conspecific sex

Ryan Remedios, Ann Kennedy, Moriel Zelikowsky, Benjamin F. Grewe, Mark J. Schnitzer, David J. Anderson

Abstract: Interactions with male and female intruders activated overlapping neuronal populations in the ventromedial hypothalamus of inexperienced adult male mice, and these ensembles gradually separated as the mice acquired social and sexual experience with conspecifics. In the laboratory, most experimentally learned animal behaviours require training to achieve high performance, with neural circuits and ensembles changing as animals master a task. However, it is not clear whether experience can influence circuits for instinctive behaviours, which can be performed without training. Here, David Anderson and colleagues report that modifications to the neural ensembles in the hypothalamus that represent sex occur with increasing social experience. They find that inexperienced animals exhibit overlapping neural representations for male or female members of the same species introduced as intruders to their cage, but sex-specific ensembles emerged over time as mice increased their social and sexual experience. The authors conclude that innate behaviours may not always function as a 'hard-wired' system. All animals possess a repertoire of innate (or instinctive1,2) behaviours, which can be performed without training. Whether such behaviours are mediated by anatomically distinct and/or genetically specified neural pathways remains unknown3,4,5. Here we report that neural representations within the mouse hypothalamus, that underlie innate social behaviours, are shaped by social experience. Oestrogen receptor 1-expressing (Esr1+) neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl) control mating and fighting in rodents6,7,8. We used microendoscopy9 to image Esr1+ neuronal activity in the VMHvl of male mice engaged in these social behaviours. In sexually and socially experienced adult males, divergent and characteristic neural ensembles represented male versus female conspecifics. However, in inexperienced adult males, male and female intruders activated overlapping neuronal populations. Sex-specific neuronal ensembles gradually separated as the mice acquired social and sexual experience. In mice permitted to investigate but not to mount or attack conspecifics, ensemble divergence did not occur. However, 30 minutes of sexual experience with a female was sufficient to promote the separation of male and female ensembles and to induce an attack response 24 h later. These observations uncover an unexpected social experience-dependent component to the formation of hypothalamic neural assemblies controlling innate social behaviours. More generally, they reveal plasticity and dynamic coding in an evolutionarily ancient deep subcortical structure that is traditionally viewed as a ‘hard-wired’ system.