Make war not love: The neural substrate underlying a state-dependent switch in female social behavior.

Female mice exhibit opposing social behaviors toward males depending on their reproductive state: virgins display sexual receptivity (lordosis behavior), while lactating mothers attack. How a change in reproductive state produces a qualitative switch in behavioral response to the same conspecific stimulus is unknown. Using single-cell RNA-seq, we identify two distinct subtypes of estrogen receptor-1-positive neurons in the ventrolateral subdivision of the female ventromedial hypothalamus (VMHvl) and demonstrate that they causally control sexual receptivity and aggressiveness in virgins and lactating mothers, respectively. Between- and within-subject bulk-calcium recordings from each subtype reveal that aggression-specific cells acquire an increased responsiveness to social cues during the transition from virginity to maternity, while the responsiveness of the mating-specific population appears unchanged. These results demonstrate that reproductive-state-dependent changes in the relative activity of transcriptomically distinct neural subtypes can underlie categorical switches in behavior associated with physiological state changes. [Display omitted] • scRNA-seq reveals distinct cell types in female VMHvl active in mating versus aggressive behaviors • Activation of VMHvl Esr1+,Npy2r− (α) cells promotes mating behaviors in virgins • Activation of VMHvl Npy2r+ (β) cells promotes aggression in both virgins and dams • Response of β, but not α, cells to male social cues increases in lactating dams Internal states can profoundly alter innate behavioral responses to releasing stimuli. Liu et al. identify distinct neural subpopulations within a single hypothalamic nucleus (VMHvl) that causally control female mating versus aggressive behaviors. Changes in the subpopulations' relative cue sensitivity underlies a state-dependent switch in social behaviors. [ABSTRACT FROM AUTHOR]