Serotonin and insulin-like peptides modulate leucokinin-producing neurons that affect feeding and water homeostasis in Drosophila

• Published in: Journal of comparative neurology (1911) Vol. 523; no. 12; pp. 1840 - 1863
• Main Authors: Liu, Yiting, Luo, Jiangnan, Carlsson, Mikael A., Nässel, Dick R.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 15.08.2015; Wiley Subscription Services, Inc
• Subjects: AB_221568; Abdomen; Animals; Animals, Genetically Modified; Appetite Regulation - physiology; Calcium - metabolism; calcium imaging; Dehydration - metabolism; Drinking Water; Drosophila; Drosophila melanogaster - metabolism; Drosophila Proteins - metabolism; Eating - physiology; Female; Functional Zoomorphology; funktionell zoomorfologi; Homeostasis - physiology; Insulin - metabolism; insulin receptor; Male; neuromodulation; Neurons - metabolism; neuropeptides; Neuropeptides - metabolism; Organ Size; Peptides - metabolism; Receptor, Serotonin, 5-HT1B - metabolism; RRID; RRID: AB_221568; RRID: AB_221570; RRID: AB_2341169; serotonin receptor; Starvation - metabolism; neuromodulation; serotonin receptor; AB_221568; RRID: AB_2341169; neuropeptides; insulin receptor; RRID; calcium imaging; RRID: AB_221570
• ISSN: 0021-9967; 1096-9861; 1096-9861
• DOI: 10.1002/cne.23768

Metabolic homeostasis and water balance is maintained by tight hormonal and neuronal regulation. In Drosophila, insulin‐like peptides (DILPs) are key regulators of metabolism, and the neuropeptide leucokinin (LK) is a diuretic hormone that also modulates feeding. However, it is not known whether LK and DILPs act together to regulate feeding and water homeostasis. Because LK neurons express the insulin receptor (dInR), we tested functional links between DILP and LK signaling in feeding and water balance. Thus, we performed constitutive and conditional manipulations of activity in LK neurons and insulin‐producing cells (IPCs) in adult flies and monitored food intake, responses to desiccation, and peptide expression levels. We also measured in vivo changes in LK and DILP levels in neurons in response to desiccation and drinking. Our data show that activated LK cells stimulate diuresis in vivo, and that LK and IPC signaling affect food intake in opposite directions. Overexpression of the dInR in LK neurons decreases the LK peptide levels, but only caused a subtle decrease in feeding, and had no effect on water balance. Next we demonstrated that LK neurons express the serotonin receptor 5‐HT1B. Knockdown of this receptor in LK neurons diminished LK expression, increased desiccation resistance, and diminished food intake. Live calcium imaging indicates that serotonin inhibits spontaneous activity in abdominal LK neurons. Our results suggest that serotonin via 5‐HT1B diminishes activity in the LK neurons and thereby modulates functions regulated by LK peptide, but the action of the dInR in these neurons remains less clear. J. Comp. Neurol. 523:1840–1863, 2015. © 2015 Wiley Periodicals, Inc. A set of neurosecretory cells (ABLKs) that express the peptide leucokinin are shown to regulate water homeostasis and feeding in Drosophila. Insulin and serotonin receptors expressed by the ABLKs modulate their activity and affect aspects of the fly's physiology.