Neprilysin 1 in the Mushroom Body controls Feeding behavior by regulating SIFamide levels in Drosophila melanogaster

Abstract

Feeding-related behavior in Drosophila melanogaster encompasses olfactory and gustatory detection of odors, foraging, and food intake. In Drosophila melanogaster, the neuropeptide SIFamide (SIFa), has been shown to integrate hunger signals to promote feeding in Drosophila and is considered a central regulator of mutually exclusive behavioral states. Here, we identify the mushroom bodies as a key downstream circuit of SIFamidergic neurons for regulation of food-seeking and feeding. Furthermore, we show that mushroom bodies are not merely downstream effectors but actively shape SIFamidergic signaling through the peptidase Neprilysin 1 for which SIFamide is a substrate. Thus, SIFa signaling is embedded within a feedforward-feedback circuit that couples internal state to the selection and execution of feeding behavior. We propose that the distinct neuronal subtypes postsynaptic to the elaborately arborized SIFamidergic neurons define discrete neuronal subroutines that differentially control the mutually exclusive behaviors related to sexual reproduction, sleep and feeding. Our findings reveal an evolutionary ancient peptidergic system that is modified by recruitment of novel genes for the flexible control of distinct behavioral programs and feeding strategies.