Allatostatin A Signalling in Drosophila Regulates Feeding and Sleep and Is Modulated by PDF

Abstract

Feeding and sleep are fundamental behaviours with significant interconnections and cross-modulations. The circadian system and peptidergic signals are important components of this modulation, but still little is known about the mechanisms and networks by which they interact to regulate feeding and sleep. We show that specific thermogenetic activation of peptidergic Allatostatin A (AstA)-expressing PLP neurons and enteroendocrine cells reduces feeding and promotes sleep in the fruit fly Drosophila. The effects of AstA cell activation are mediated by AstA peptides with receptors homolog to galanin receptors subserving similar and apparently conserved functions in vertebrates. We further identify the PLP neurons as a downstream target of the neuropeptide pigment-dispersing factor (PDF), an output factor of the circadian clock. PLP neurons are contacted by PDF-expressing clock neurons, and express a functional PDF receptor demonstrated by cAMP imaging. Silencing of AstA signalling and continuous input to AstA cells by tethered PDF changes the sleep/activity ratio in opposite directions but does not affect rhythmicity. Taken together, our results suggest that pleiotropic AstA signalling by a distinct neuronal and enteroendocrine AstA cell subset adapts the fly to a digestive energy-saving state which can be modulated by PDF.

Author Summary

Feeding and sleep are fundamental behaviours that are controlled by diverse neuropeptides. While feeding is associated with wake periods, sleep prevents feeding. Both feeding and sleep are timed to specific parts of the day by internal clocks, presumably to optimise behaviour and metabolic processes. We investigated the functions of Allatostatin A (AstA) peptides in the fruit fly. AstA is produced by neurons as well as by endocrine cells in the midgut epithelium. Thermogenetic activation of subsets of AstA-producing cells in the brain and midgut revealed that AstA affects both feeding and sleep in opposite directions: feeding is reduced by AstA signalling, while sleep is promoted. Others could previously show that insect AstA also inhibits gut motility and release of digestive enzymes from the gut. An attractive conclusion is that AstA signalling helps to put flies in a digestive energy-saving state. Interestingly, a set of six AstA-expressing PLP neurons are in close contact to neurons central to the circadian clock network, and express functional receptors for the clock output signal PDF. This opens the possibility that PLP neurons are at the interface between clock, feeding and sleep—a hypothesis that needs to be tested in the future.