Riemensperger, T. | Search bioRxiv

bioRxiv2026

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

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.

animal behavior and cognition↗

bioRxiv2019

Transneuronal interactions facilitate axonal compartment formation

The mechanisms controlling wiring of neuronal networks are largely unknown. The stereotypic architecture of the Drosophila mushroom-body (MB) offers a unique system to study circuit assembly. The adult medial MB {gamma}-lobe is comprised of a long bundle of axons that wires with specific modulatory and output neurons in a tiled manner defining five distinct zones. We found that the immunoglobulin superfamily protein Dpr12 is cell-autonomously required in {gamma}-neurons for their developmental regrowth into the distal {gamma}4/5 zones, where both Dpr12 and its interacting protein, DIP-{delta}, are enriched. DIP-{delta} functions in a subset of dopaminergic neurons that wire with {gamma}-neurons within the {gamma}4/5 zone. During metamorphosis, these dopaminergic projections arrive to the {gamma}4/5 zone prior to {gamma}-axons, suggesting that {gamma}-axons extend through a prepatterned region. Thus, Dpr12/DIP-{delta} transneuronal interaction is required for {gamma}4/5 zone formation. Our study sheds light onto molecular and cellular mechanisms underlying circuit formation within subcellular resolution.

neuroscience↗