Octopamine-mediated circuit mechanism underlying controlled appetite for palatable food in Drosophila

Abstract

The easy accessibility of energy-rich palatable food makes it difficult to resist food temptation. Drosophila larvae are surrounded by sugar-rich food most of their lives, raising the question of how these animals modulate food-seeking behaviors in tune with physiological needs. Here we describe a circuit mechanism defined by neurons expressing tdc2-Gal4 (a tyrosine decarboxylase 2 promoter-directed driver) that selectively drives a distinct foraging strategy in food-deprived larvae. Stimulation of this otherwise functionally latent circuit in tdc2-Gal4 neurons was sufficient to induce exuberant feeding of liquid food in fed animals, whereas targeted lesions in a small subset of tdc2-Gal4 neurons in the subesophageal ganglion blocked hunger-driven increases in the feeding response. Furthermore, regulation of feeding rate enhancement by tdc2-Gal4 neurons requires a novel signaling mechanism involving the VEGF2-like receptor, octopamine, and its receptor. Our findings provide fresh insight for the neurobiology and evolution of appetitive motivation. T he adaptive control of foraging decisions is crucial to survival and reproduction and is mediated by complex brain mechanisms. For example, in hungry animals, feeding behaviors can be modulated by diverse neural systems including those responsible for receiving and processing sensory properties and assigning reward and motivational significance of food stimuli (1-3). At present, elucidation of molecular and circuit mechanisms underlying the adaptive control of feeding behavior remains highly challenging.Our previous studies have shown that Drosophila larvae, like mammals, display diverse adaptive foraging strategies in response to appetizing odors or satiety state and food quality (4-6). For example, larvae fed for ad libitum intake tend to prefer soft, liquid sugar media that contain readily ingestible sugar solution but decline solid media in which sugar solution is embedded in gelled agar and is less accessible (5). However, as food deprivation is prolonged, larvae will become increasingly persistent in extracting the sugar solution from solid media (7). We have also shown that an evolutionarily conserved signaling cascade, involving neuropeptide F (NPF, the fly homolog of neuropeptide Y, or NPY) and insulin-like peptides (dILPs), selectively integrates motivational state (hunger) with persistence to pulverize solid food (5, 7).The observation that the conserved NPY-like system selectively promotes food acquisition behaviors that require high energetic cost has led us to postulate that fly larvae may use other conserved neural mechanisms to regulate acquisition of readily accessible palatable food. In this work, we provide evidence which supports this hypothesis. We show that an octopamine (OA)/β-adrenergic-like receptor (Octß3R)-dependent circuit mechanism selectively regulates appetite for soft sugar media. This circuit mechanism seems to involve two subsets of tdc2-Gal4 neurons in the subesophogeal ganglia (SOG). One of them mediates the hunger-driven increase ...

Induction of Associative Olfactory Memory by Targeted Activation of Single Olfactory Neurons in Drosophila Larvae

“…The Tdc2 promoter sequence utilized in this construct has been characterized to drive specific expression in the larval OA neurons21819. Whereas control larvae preferred cooler temperature, transgenic larvae carrying the Tdc2-dTrpA1 construct showed positive thermotactic response when assayed on a 21–28°C temperature gradient (Figure 2 and Supplemental Movies 1, 2).…”

“…Genomic sequence containing a region from -3459 to +4530 of the dTdc2 locus was amplified through stepwise PCR and cloned into pCaSpeR4. Previous studies21819 demonstrated that this element drives specific expression in the larval OA neurons. A 3.6 kb DNA fragment containing the coding region of dTrpA110 (gift from Paul Garrity) tagged with HA was inserted upstream of the dTdc2 coding sequence17.…”

Obesity-Linked Homologues TfAP-2 and Twz Establish Meal Frequency in Drosophila melanogaster

“…Here we demonstrate that specifically activating octopaminergic neurons using a bacterial sodium channel is sufficient to induce hyperphagia (see figure 4C and 4D). Also, a recent study demonstrated that octopamine signaling induced fervent feeding behavior when larvae were presented with palatable food [13]. Furthermore, it was shown that Dsk is necessary to inhibit well-fed larvae or adults from eating less palatable foods [12].…”

Drk-mediated signaling to Rho kinase is required for anesthesia-resistant memory in Drosophila

“…Therefore, we sought to determine whether Drk is required for ARM within the MBs or other adult brain structures. MB-specific Drk abrogation was achieved with transgenes (drkR-1.2), shown to effectively knock down its levels (17,20) via RNA-mediated interference (RNAi).…”