Sex peptide targets distinct higher order processing neurons in the brain to induce the female post-mating response

Sex peptide (SP) transferred during mating induces female post-mating responses including refractoriness to re-mate and increased oviposition in Drosophila. Yet, where SP-target neurons reside remained uncertain. Here, we show that expression of membrane-tethered SP (mSP) predominantly in the head or trunk either reduces receptivity or increases oviposition, respectively. Using fragments from large regulatory regions of Sex Peptide Receptor, fruitless, and doublesex genes together with intersectional expression of mSP, we identified distinct interneurons in the brain and abdominal ganglion controlling receptivity and oviposition. These SP response-inducing neurons (SPRINz) can induce post-mating responses through SP received by mating. Trans-synaptic mapping of neuronal connections reveals input from sensory processing neurons and two post-synaptic trajectories as output. Hence, SP-target neurons operate as key integrators of sensory information for decision-making of behavioural outputs. Multi-modularity of SP-targets further allows females to adjust SP-mediated male manipulation to physiological state and environmental conditions for maximising reproductive success.