Females of many animal species behave very differently before and after mating. In Drosophila melanogaster, changes in female behavior upon mating are triggered by the sex peptide (SP), a small peptide present in the male's seminal fluid. SP activates a specific receptor, the sex peptide receptor (SPR), which is broadly expressed in the female reproductive tract and nervous system. Here, we pinpoint the action of SPR to a small subset of internal sensory neurons that innervate the female uterus and oviduct. These neurons express both fruitless (fru), a marker for neurons likely to have sex-specific functions, and pickpocket (ppk), a marker for proprioceptive neurons. We show that SPR expression in these fru+ ppk+ neurons is both necessary and sufficient for behavioral changes induced by mating. These neurons project to regions of the central nervous system that have been implicated in the control of reproductive behaviors in Drosophila and other insects.

Mating induces pronounced changes in female reproductive behavior, typically including a dramatic reduction in sexual receptivity. In Drosophila, postmating behavioral changes are triggered by sex peptide (SP), a male seminal fluid peptide that acts via a receptor (SPR) expressed in sensory neurons (SPSNs) of the female reproductive tract. Here, we identify second-order neurons that mediate the behavioral changes induced by SP. These SAG neurons receive synaptic input from SPSNs in the abdominal ganglion and project to the dorsal protocerebrum. Silencing SAG neurons renders virgin females unreceptive, whereas activating them increases the receptivity of females that have already mated. Physiological experiments demonstrate that SP downregulates the excitability of the SPSNs, and hence their input onto SAG neurons. These data thus provide a physiological correlate of mating status in the female central nervous system and a key entry point into the brain circuits that control sexual receptivity.