Feeding decisions are tightly regulated based on internal needs. Signals of hunger and thirst are detected by interoceptive neurons that promote specific consumption to restore homeostasis. Although generally considered independently, recent studies have demonstrated that interactions between hunger and thirst drives are important to coordinate competing needs. The aim of this proposal is to examine how food and water consumption is coordinately regulated, using the well developed Drosophila system as a model. These studies will evaluate how multiple internal signals are integrated within a neuron to regulate activity and how the activity of a single set of neurons regulates two opponent behaviors. This research takes advantage of established behavioral assays for water and sucrose consumption in Drosophila, molecular genetics to rapidly manipulate genes and neural function, single-cell electrophysiology for precise measurements of signal integration, and large-scale calcium imaging approaches to study network interactions. Specific Aim 1 will examine how signals of hunger and thirst modulate activity of interoceptive neurons, providing insight into how multiple signals are integrated within a neuron over time. Specific Aim 2 will characterize neurons downstream of the interoceptive neurons to examine how activity is transmitted to circuits to oppositely regulate two behaviors. Specific Aim 3 will determine how interoceptive neurons alter the responses in taste sensorimotor circuits to examine how internal states generate plastic changes in feeding networks. The proposed efforts will determine how internal signals of nutritional state are integrated across time to coordinate feeding decisions. The long-term objective of this work is to provide insight into how neuromodulators regulate circuits and behavior over long timescales, a basic problem in neuroscience relevant across systems.