Allatostatin-A neurons inhibit feeding behavior in adult Drosophila

How the brain translates changes in internal metabolic state or perceived food quality into alterations in feeding behavior remains poorly understood. Studies in Drosophila larvae have yielded information about neuropeptides and circuits that promote feeding, but a peptidergic neuron subset whose activation inhibits feeding in adult flies, without promoting metabolic changes that mimic the state of satiety, has not been identified. Using genetically based manipulations of neuronal activity, we show that activation of neurons (or neuroendocrine cells) expressing the neuropeptide allatostatin A (AstA) inhibits or limits several starvation-induced changes in feeding behavior in adult Drosophila, including increased food intake and enhanced behavioral responsiveness to sugar. Importantly, these effects on feeding behavior are observed in the absence of any measurable effects on metabolism or energy reserves, suggesting that AstA neuron activation is likely a consequence, not a cause, of metabolic changes that induce the state of satiety. These data suggest that activation of AstA-expressing neurons promotes food aversion and/or exerts an inhibitory influence on the motivation to feed and implicate these neurons and their associated circuitry in the mechanisms that translate the state of satiety into alterations in feeding behavior

Nutrient Sensor in the Brain Directs the Action of the Brain-Gut Axis in Drosophila

Animals can detect and consume nutritive sugars without the influence of taste. However, the identity of the taste-independent nutrient sensor and the mechanism by which animals respond to the nutritional value of sugar are unclear. Here, we report that six neurosecretory cells in the Drosophila brain that produce Diuretic hormone 44 (Dh44), a homolog of the mammalian corticotropin-releasing hormone (CRH), were specifically activated by nutritive sugars. Flies in which the activity of these neurons or the expression of Dh44 was disrupted failed to select nutritive sugars. Manipulation of the function of Dh44 receptors had a similar effect. Notably, artificial activation of Dh44 receptor-1 neurons resulted in proboscis extensions and frequent episodes of excretion. Conversely, reduced Dh44 activity led to decreased excretion. Together, these actions facilitate ingestion and digestion of nutritive foods. We propose that the Dh44 system directs the detection and consumption of nutritive sugars through a positive feedback loop

The Role of Peptidergic Neurons in the Regulation of Satiety in Drosophila

Understanding the neural mechanisms that motivate us to eat is important because of the increasing rates of obesity and the consequential increasing rates of diabetes and cardiovascular disease in our society. The aim of this dissertation is to gain insight into the neuromodulators and neural mechanisms that regulate satiety. To do this, we turned to Drosophila melanogaster, which has been a powerful model organism to study the molecular mechanisms underlying innate animal behaviors and which exhibits many conserved elements of feeding regulation and energy homeostasis found in mammals. A common theme in animal behavior is that food deprivation modifies behavioral responses, e.g., the likelihood that an animal will accept a low-nutrient food. I manipulated the parameters of a feeding assay to screen for animals that lacked several starvation-induced feeding behaviors: increased foraging for food, increased acceptance of low-nutrient food, and increased ingestion of low-quality food. Using this feeding assay, I identified a neuronal circuit manipulation that inhibits several starvation-induced behaviors. Activation of a subset of Allatostatin-A-expressing neurons, using a novel transgenic tool that we generated, inhibits starvation-induced changes in both the acceptance and the ingestion of low-quality foods. In contrast, this circuit manipulation did not affect starvation-induced metabolic changes or foraging behavior. This suggests that we tapped into a mechanism that regulates a specific subset of starvation-induced changes in feeding behavior that is independent from general starvation-induced behavioral responses and energy metabolism. Studies in blowflies have revealed that the primary mechanism that promotes satiety is inhibitory proprioceptive feedback from the gut, but whether such a mechanism operates in Drosophila is unclear. While Allatostatin A has been implicated as a satiety factor and as a myoinhibitor in several other insects, it has no known function in Drosophila. A mechanism that promotes satiety but that does not alter energy metabolism has not previously been identified in Drosophila. I have used this circuit manipulation to better understand how a state of satiety is achieved in Drosophila, by integrating the knowledge acquired from studies in other insects with the knowledge acquired from molecular genetic manipulations in Drosophila