Development of the multisensory computations underlying flavor processing - SUMMARY Food is perceived and enjoyed through the multisensory quality of “flavor”, which involves the senses of taste and smell, but is not easily dissociated into its components. Flavor perception has a major influence on food choice and is thus directly linked to health. However, the underlying neural mechanisms remain mysterious. Previous work in humans has suggested that the brain actively combines taste and smell inputs to create our sense of flavor, and that this process depends heavily on eating experience. However, human imaging techniques lack spatial and temporal resolution to provide a mechanistic understanding of how neural circuits produce multisensory flavor representations. Moreover, people’s highly subjective eating history precludes a systematic understanding of how experience drives the development of flavor processing. To overcome these issues, the present proposal takes a unique approach to the study of flavor. Using the awake, tasting rat as an animal model allows us to directly access to the neural computations underlying flavor processing at the cellular level, and complete control over the individual’s flavor experience. The proposed hypotheses build directly on our own recent findings on cross-modal flavor processing in rat olfactory cortex, as well as decades of work on the development of multisensory computations in cortical and subcortical regions of other multisensory systems. The project comprises a coherent series of experiments that systematically seeks to provide mechanistic understanding of the neural circuits that integrate flavor-related sensory information. Specifically, we will answer the following questions: 1) What are the guiding principles by which olfactory cortical circuits integrate taste and smell inputs? To address this, we will use electrophysiological techniques to record responses from olfactory cortical neurons to taste-smell mixtures as well as their unisensory components in awake adult rats; 2) How are the multisensory operations performed by olfactory cortical circuits shaped by experience with specific flavors? To address this, we will experimentally manipulate rats’ experience with specific taste-smell mixtures, and record responses from ensembles of olfactory cortical neurons to congruent, incongruent and unexposed taste-smell mixtures as well as their unisensory components; and 3) How does the ability to integrate cross-modal inputs develop across the lifespan? To address this, we will track uni- and cross-modal responsiveness of olfactory cortex in awake rats across different stages of early postnatal development; To successfully achieve these objectives, our unique team of investigators brings together expertise in flavor processing and awake rodent olfactory cortex physiology (PI Maier), the computational basis of multisensory interactions (Co-I Rowland), and the development of multisensory systems (Co-I Stein).