Long-term neuropeptide modulation of female sexual drive via the TRP channel in Drosophila melanogaster.

Connectomics research has made it more feasible to explore how neural circuits can generate multiple outputs. Female sexual drive provides a good model for understanding reversible, long-term functional changes in motivational circuits. After emerging, female flies avoid male courtship, but they become sexually receptive over 2 d. Mating causes females to reject further mating for several days. Here, we report that pC1 neurons, which process male courtship and regulate copulation behavior, exhibit increased CREB (cAMP response element binding protein) activity during sexual maturation and decreased CREB activity after mating. This increased CREB activity requires the neuropeptide Dh44 (Diuretic hormone 44) and its receptors. A subset of the pC1 neurons secretes Dh44, which stimulates CREB activity and increases expression of the TRP channel Pyrexia (Pyx) in more pC1 neurons. This, in turn, increases pC1 excitability and sexual drive. Mating suppresses pyx expression and pC1 excitability. Dh44 is orthologous to the conserved corticotrophin-releasing hormone family, suggesting similar roles in other species.

Male cuticular pheromones stimulate removal of the mating plug and promote re-mating through pC1 neurons in Drosophila females.

In birds and insects, the female uptakes sperm for a specific duration post-copulation known as the ejaculate holding period (EHP) before expelling unused sperm and the mating plug through sperm ejection. In this study, we found that Drosophila melanogaster females shortens the EHP when incubated with males or mated females shortly after the first mating. This phenomenon, which we termed male-induced EHP shortening (MIES), requires Or47b+ olfactory and ppk23+ gustatory neurons, activated by 2-methyltetracosane and 7-tricosene, respectively. These odorants raise cAMP levels in pC1 neurons, responsible for processing male courtship cues and regulating female mating receptivity. Elevated cAMP levels in pC1 neurons reduce EHP and reinstate their responsiveness to male courtship cues, promoting re-mating with faster sperm ejection. This study established MIES as a genetically tractable model of sexual plasticity with a conserved neural mechanism.

A sexually transmitted sugar orchestrates reproductive responses to nutritional stress.

Seminal fluid is rich in sugars, but their role beyond supporting sperm motility is unknown. In this study, we found Drosophila melanogaster males transfer a substantial amount of a phospho-galactoside to females during mating, but only half as much when undernourished. This seminal substance, which we named venerose, induces an increase in germline stem cells (GSCs) and promotes sperm storage in females, especially undernourished ones. Venerose enters the hemolymph and directly activates nutrient-sensing Dh44+ neurons in the brain. Food deprivation directs the nutrient-sensing neurons to secrete more of the neuropeptide Dh44 in response to infused venerose. The secreted Dh44 then enhances the local niche signal, stimulating GSC proliferation. It also extends the retention of ejaculate by females, resulting in greater venerose absorption and increased sperm storage. In this study, we uncovered the role of a sugar-like seminal substance produced by males that coordinates reproductive responses to nutritional challenges in females.