Saturday, May 10, 2025
5/10/2025
Dissecting the first layer of central taste processing in Drosophila - Our sense of taste is critical in helping us decide what to eat. Altered taste perception is associated with obesity and eating disorders, suggesting that dysregulation of taste processing may contribute to these conditions. Understanding how the taste system flexibly transforms sensory input into behavior thus represents a fundamental question underlying feeding decisions across healthy and disordered states. Two key questions underpin the mechanisms of taste processing: how are neuronal responses to taste transformed along the taste pathway, and how do these responses drive behavior? Studies in mammalian models have characterized neuronal responses at each layer of the taste system, but it is not clear how these neuronal responses are used to drive behavioral responses to taste. To address this gap, this proposal uses a model system, Drosophila melanogaster, that offers unique tools to examine the connectivity, response properties, and behavioral role of individual cell types within each layer of taste processing. For decades, central taste circuits in Drosophila have remained largely unknown. Recent studies by our lab and others have identified neurons that receive direct input from taste sensory cells, termed second-order neurons, which represent the first layer of taste processing in the brain. These second-order neurons include diverse types of taste projection neurons (TPNs) that relay taste information to higher brain regions. The goal of this proposal is to determine how TPNs, both individually and as a population, transform sensory information and regulate behavior. Our central hypothesis is that different types of TPNs encode different features of taste and make distinct contributions to behavior, representing parallel pathways for sensory processing. In Aim 1 we will use in vivo two-photon calcium imaging to determine how each type of TPN encodes and transforms sensory information. We will test response properties such as taste selectivity, dose-dependence, response dynamics, and hunger-dependent modulation. In Aim 2 we will examine how the information encoded by TPNs is used to drive behavior. We will activate or silence each TPN type and examine the effect on a range of taste-related behaviors, including feeding, locomotion, spatial preference, and learning. These experiments will determine whether different TPN types represent separate pathways for regulating different aspects of behavior, or whether TPN outputs converge downstream to regulate a common set of behaviors. In addition to analyzing each TPN type individually, we will use computational modeling to examine how activity across the TPN population is transformed into behavior. Together, these studies will reveal how taste encoding is transformed at the first synapse and distributed across diverse cell types, and how these neuronal responses are used to drive specific behaviors. Given the similarities in how flies and mammals respond to taste, we expect to uncover fundamental principles that generalize to other species. Understanding taste processing also lays the groundwork to investigate how the dysregulation of taste circuits contributes to overeating and obesity.
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