Drosulfakinin signaling modulates female sexual receptivity in Drosophila

Abstract

Female sexual behavior as an innate behavior is of prominent biological importance for survival and reproduction. However, molecular and circuit mechanisms underlying female sexual behavior is not well understood. Here, we identify the Cholecystokinin-like peptide Drosulfakinin (DSK) to promote female sexual behavior in Drosophila. Loss of DSK function reduces female receptivity while overexpressing DSK enhances female receptivity. We identify two pairs of Dsk-expressing neurons in the central brain to promote female receptivity. We find that the DSK peptide acts through one of its receptors, CCKLR-17D3, to modulate female receptivity. Manipulation of CCKLR-17D3 and its expressing neurons alters female receptivity. We further reveal that the two pairs of Dsk-expressing neurons receive input signal from pC1 neurons that integrate sex-related cues and mating status. These results demonstrate how a neuropeptide pathway interacts with a central neural node in the female sex circuitry to modulate sexual receptivity.

Sex peptide regulates female receptivity through serotoninergic neurons in Drosophila

“…In the brain, multiple types of neurons have been suggested to regulate virgin female receptivity. 4 , 6 , 7 , 10 , 11 , 64 Except for the R2/R4m and R4d neurons in the ellipsoid body, the locations of other neurons did not seemingly associate sexual receptivity with prominent structures. 10 When we used the split-Gal4 approach to attribute the behavioral effects to smaller groups of responsible neurons, we identified a subset of 5-HT neurons (MB002B) that predominately project into particular compartments of the β′ or γ lobe of the mushroom body.…”

“…Our results suggest an additional regulatory pathway triggered by SP, and that this pathway starts in the brain where SP targets a pair of 5-HT neurons, and that SPN plays an important role in regulating virgin receptivity: activating SPN elevates female receptivity whereas silencing SPN decreases female receptivity. Although multiple neurons have been reported to play regulatory roles in virgin female receptivity, 2 , 4 , 6 , 7 , 10 , 11 , 17 , 18 , 19 , 21 , 22 , 64 only manipulations in subsets of dsx -positive neurons (including pCd, pC1), DSK neurons, dopamine neurons and their downstream R2/R4m neurons, together with serotoninergic neurons upregulated receptivity in virgin females, suggesting distinct pathways to regulate receptivity in virgin and mated females. Furthermore, material transfer during copulation, rather than the courtship experience itself, renders a decreased activity in SPN.…”

“… 8 , 9 The neurotransmitter dopamine and neural peptides Drosulfakinin (DSK) have been investigated for their roles in regulating female receptivity. 10 , 11 The residing neurons and corresponding receptors have also been revealed, and DSK neurons are direct targets of pC1 neurons. 11 Outside the brain, neurons in the abdominal ganglion and genitalia, particularly the Abd-B neurons, promote pausing in virgin females.…”

“… 10 , 11 The residing neurons and corresponding receptors have also been revealed, and DSK neurons are direct targets of pC1 neurons. 11 Outside the brain, neurons in the abdominal ganglion and genitalia, particularly the Abd-B neurons, promote pausing in virgin females. 2 …”

The impact of social isolation on health and behavior inDrosophila melanogasterand beyond

“…Drosulfakinin (Dsk) is a Drosophila homolog of vertebrate cholecystokinin, a protein known to modulate aggression and social behavior in mice and other mammals. In fruit flies, Dsk modulates sexual arousal and fighting behavior [68][69][70]. Agrawal et al established the neuropeptide Dsk as a regulator of isolation-induced aggression in D. melanogaster [28].…”