PROJECT SUMMARY: Animals constantly detect different environmental stimuli and change their behavior or physiology based on their internal state. How animals integrate the external multiple sensory information with the internal state is largely unclear. The specific goal of this proposal is to explore the neural circuits and mechanisms of internal state- dependent modulation of multiple sensory integrations. We will draw on a powerful, versatile, and relatively simple genetic model, Drosophila, to address the neural mechanisms of taste-temperature integration. We recently identified a new cephalic phase response (CPR) caused by taste-temperature integration. CPR is rapid and partial recovery from the starved state and is a robust and typical response for many animals, including humans. When animals are hungry, the sensory detection of food elicits bursts of physiological changes in their bodies; this rapid response is CPR. Our primary data suggest that taste-temperature integration leads to CPR in flies. In this R34 application, we will explore how taste-temperature integration is regulated by using CPR as output. We will examine neural mechanisms of taste-temperature integration by monitoring taste- and temperature-processing neuronal activity using calcium imaging. Furthermore, hunger signals such as Drosophila neuropeptide F, a homolog of mammalian neuropeptide Y, are critical for CPR, suggesting that hunger signals modulate the taste-temperature neural circuits. These preliminary data lead to our central hypothesis: hunger signals modulate the sensory integration between taste- and temperature-processing neurons, which drives CPR. The following two specific aims are proposed: In Aim 1, we will explore the neural mechanisms and circuits of taste-temperature integration. In Aim 2, we will explore the mechanisms by which the internal state modulates taste-temperature integration.