PROJECT SUMMARY Aberrant food seeking and food consumption are a common characteristic among individuals suffering from eating disorders; however, the underlying mechanisms controlling food seeking have yet to be conclusively identified. The paraventricular nucleus of the thalamus (PVT) has recently emerged as a key brain region that integrates homeostatic signals originating in the lateral hypothalamus (LH) to promote adaptive responses via projections to the Nucleus Accumbens (NAcc). Several lines of evidence suggest that the PVT may balance food seeking and food consumption. However, despite this evidence, the neural mechanisms underlying the involvement of the PVT in food seeking and food consumption remain largely unknown. Our goal is to define the role of the PVT in food seeking and food consumption. Previous work and our preliminary data show that both food restriction and food-associated cues lead to PVT activation. Moreover, food presentation and food consumption reduce the activity of NAcc-projecting PVT neurons. My central hypothesis is that activation of NAcc-projecting PVT neurons is required for food seeking and subsequent inhibition of these neurons is required to terminate food seeking and permit food consumption. Specifically, we propose that excitatory projections to the PVT from the glutamatergic/orexinergic neurons of the LH (LHglu/orexin) promote food seeking behavior. Then, inhibition of PVT neurons, via projections from the GABAergic neurons in the LH (LHGABA) during food presentation, is needed to promote food consumption. This hypothesis will be addressed in two specific aims: In Aim 1, we will first determine whether bidirectional changes in PVT activity are required for optimal performance in a cue-induced food seeking task. Then, we will determine the role of excitatory inputs from LHglu/orexin neurons in activation of the PVT during hunger to drive food seeking. Lastly, in aim 2, we aim to establish the role of inhibitory inputs from LHGABA neurons in inhibition of the PVT during food presentation to allow for food seeking. The experiments will use contemporary molecular, biological, in vivo fiber photometry imaging and behavioral tasks to test the hypotheses. Execution of these aims will provide training in contemporary approaches to studying the neural circuitry underlying food seeking and food consumption. I will also supplement my molecular and biological training with slice physiology. These findings will advance our understanding of the neural circuits promoting food seeking and food consumption that can aid with the development of new approaches for treatments of individuals suffering from eating disorders.!