Circuit Mechanisms of Cross-Organ Taste Integration for Feeding in Drosophila

PROJECT SUMMARY We integrate sensory signals, like smell and taste, to make decisions about the type and quantity of food to eat on a daily basis. Distinct sensory inputs converge in brain regions that regulate food intake, such as the gustatory cortex, but the neural circuit mechanisms that integrate sensory information to control food consumption remain largely unknown. The fruit fly Drosophila melanogaster provides an excellent model system to address this question, as we can genetically target individual neurons in the fly brain and use the whole-brain connectome to identify pathways linking sensory input to motor output. Just as humans use multiple sensory cues to evaluate the quality of food, flies use distinct taste inputs from their legs and feeding organ, the proboscis, to decide whether to initiate feeding. This study will determine where and how neural circuits in the fly brain integrate concurrent taste input from the legs and proboscis to regulate feeding, providing a model to more broadly understand the logic of how neural circuits integrate different food-related signals. The experiments in Aim 1 will determine how sugar inputs on the legs and proboscis are integrated to regulate the likelihood that flies will initiate feeding and the quantity of food they consume. In vivo calcium imaging experiments in Aim 2 will determine how concurrent sugar input on the legs and proboscis influences the activity of individual neurons in a neural circuit known to respond to sugar and promote feeding initiation. These recordings of neural activity, combined with an analysis of neuronal connectivity in the whole-brain connectome, will provide a neural substrate for the behavior identified in Aim 1. Together, the findings from this study will identify the neural circuit mechanisms that integrate distinct taste inputs to promote adaptive feeding behavior. The basic principles of chemosensory processing and its role in feeding regulation are conserved across species. Thus, future work can use our findings to develop hypotheses about the neural circuits that combine sensory cues to regulate food consumption— and investigate whether these circuits contribute to dysregulated eating— in rodents and humans.