PROJECT SUMMARY Immune challenges engage neural circuits to evoke stereotyped behavioral and physiological responses. For example, infections evoked neuronally orchestrated sickness symptoms that include fever, lethargy, decreased appetite, nausea, and cough. Likewise, allergic reactions and anaphylaxis evoke neuronal responses that include nausea, cardiorespiratory changes, and sensations of discomfort and pain. Despite their medical importance, little is understood about (1) how the brain detects the presence of an allergen, (2) what neural circuits are engaged, and (3) what sympathetic and parasympathetic motor programs control autonomic physiology and immune responses. In this project, we will chart communication mechanisms between the immune and nervous systems that underlie neuronal responses to allergens. We have assembled an expansive genetic toolkit to study neurons involved in neuro-immune crosstalk and the gut-brain axis. We will use state-of-the-art neurogenetic approaches such as optogenetics, chemogenetics, in vivo imaging, fiber photometry, targeted neuron ablation, and anatomical mapping to study the role of allergen-activated neural circuits roles in physiology and behavior. We hypothesize that specific sensory and motor neuron types contribute to food allergen-evoked behavioral and physiological changes. Characterizing allergen-activated neurons will provide an essential foundation for mechanistic study and potentially therapy design.