PROJECT SUMMARY Recent studies on the gustatory portion of the insular cortex (gustatory cortex, GC) have demonstrated its role in integrating sensory, affective, and cognitive signals associated with the experience of food. Indeed, GC neurons do not just encode the chemosensory features of gustatory stimuli but can also process hedonic value (i.e. liking or disliking) and information on multisensory stimuli anticipating taste. Understanding how GC performs the complex integration of chemosensory, affective, and anticipatory information is one of the major efforts in the field. It is generally believed that GC achieves this level of integration by processing inputs from sensory and limbic areas including the gustatory thalamus (VPMpc), the basolateral amygdala (BLA), and the mediodorsal thalamic nuclei (MD). While the functions of VPMpc and BLA have been studied, very little is known regarding the contribution of MD in taste. Using mice as a model system, the proposed research will rely on multiple experimental approaches to test the general hypothesis that the MD conveys taste quality, reward-related, and associative signals that contribute to processes in the GC that can impact taste-related behaviors. Specific Aim 1 will use electrophysiological recordings and behavioral training to characterize the taste and taste-predicting cues response profile in the MD. Specific Aim 2 will combine neural recordings, behavioral training and chemogenetic manipulation to unveil the effect of MD inputs on GC response profiles pertaining to taste quality and taste-predicting anticipatory cues. Finally, the experiment in Specific Aim 3 will rely on a behavioral task and chemogenetic manipulation to determine the role of the MD-GC connection in helping to establish incentive values of neutral auditory cues in the acquisition of cue-taste associations. Altogether, the results obtained from these experiments will provide a comprehensive system-level investigation on the role of MD in taste processing. If successful, this work will lead the way for the MD thalamus as a potential crucial brain region involved in the integration and communication of behaviorally relevant chemosensory information.