A Neuropeptidergic Neural Network Integrates Taste with Internal State to Modulate Feeding

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Feeding is a fundamental behavior that is tightly regulated to precisely meet the metabolic needs of the animal. The primary decision that an animal must make regarding food is whether to ingest it or reject it. Substances with high nutritional value are ingested, while toxins and harmful substances are rejected. To make this decision, the animal relies on its sense of taste to evaluate the quality of the food. Most animals respond to sweet and bitter tastants with different stereotyped behaviors: sweet substances, often calorie rich, are appetitive and accepted, while bitter compounds, usually harmful, are rejected and avoided. Another important part of the decision whether to ingest or reject potential food is the metabolic need of the animal that is manifested by the balance between hunger and satiety. This aspect of the internal state of the animals is evaluated through an intricate balance between various hormones and neuromodulators, some signal hunger while the others signal satiety. How the concerted action of the various hormones and neuromodulators affects feeding is an area of significant interest as dysregulation of feeding behavior results in obesity or in malnutrition and their associated morbidities. In this proposal, we focus on one network of neuromodulatory neurons in Drosophila in which a neuromodulator termed leucokinin is secreted by certain subsets of neurons within the network and detected by others. We propose to test the hypothesis that the leucokinin network of neuromodulatory neurons integrates information about taste quality and the internal state of the fly to modulates feeding behavior. In this network, one set of neurons receives inputs from two others: taste information from one, and information about the internal state of the animal from the other. The recipient neurons integrate the two streams of information and in turn modulate feeding behavior by secreting other neuropeptides that regulate feeding. To test this hypothesis, we use a multipronged approach that includes anatomical, functional and behavioral analyses. In our proposed study, we use state of the art techniques to label neuronal connectivity and to manipulate the activity of selective subsets of neurons to examine the behavioral and functional effects of these manipulations. We also develop a new technique for studying sites of neuromodulation. This technique enables selective, unbiased, brain-wide examination of sites of neuromodulation by specific modulators with cellular resolution. Thus, our studies will deepen our understanding of the regulation of feeding and provide new tools to study neuromodulation, a research area that will increase in importance as neural connectivity maps of more model organisms become available.