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.

Drosophila Neuropeptide F Signaling Independently Regulates Feeding and Sleep-Wake Behavior

“…Furthermore, co-expression with the pan-neuronal GAL4 repressor nSyb-GAL80 (Rezaval et al, 2012) completely reverted the increased wake phenotype caused by NPF cell activation (Figure S2C). It has been reported that nSyb-GAL80 blocks GAL4 expression both in the nervous system (Rezaval et al, 2012) and AstA- producing EECs (Chen et al, 2016). However, in our hands, nSyb-GAL80 successfully blocked NPF-GAL4 reporter expression in the adult brain, but failed to completely repress expression in the EECs (Figure S2D).…”

“…Diet-mediated effects on sleep-wake behavior rely on gustatory receptors that converge onto the SOG (Linford et al, 2012), and NPF activity within the SOG may play a role in this response. Beyond the CNS, midgut NPF + EEC effects on nutrient evaluation or feeding cannot be completely ruled out, and both published findings and the data presented leaves open the possibility that the gut-brain axis may utilize neuropeptide signaling, which may include NPF, to properly synchronize feeding with wakefulness (Chen et al, 2016). …”

Neuropeptide relay between SIFa signaling controls the experience-dependent mating duration of male Drosophila

“…This process is also facilitated through AstA-AKH interactions to maintain the dynamic balance of glucose. AstA is a neuropeptide involved in a series of satiety signals such as feeding, metabolism, and sugar reward [50][51][52]. Its receptor, Allatostatn A Receptor (AstAR), is expressed in both insulin and AKH cells.…”

Drosophila neprilysins control insulin signaling and food intake via cleavage of regulatory peptides

“…Interestingly, corazonin promotes food intake (Hergarden et al, 2012), while allatostatin A and drosulfakinins inhibit it (Hergarden et al, 2012; Söderberg et al, 2012; Chen et al, 2016). This regulatory activity on peptides with opposing physiological functions indicates that Nep4 affects multiple aspects of feeding control, rather than promoting or inhibiting food intake in a mutually exclusive manner.…”