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) 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 interneurons 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 of behavioural outputs. Multi-modularity of SP targets further allows females to adjust SP-mediated male manipulation to physiological state and environmental conditions for maximizing reproductive success.