PROJECT SUMMARY/ABSTRACT Environmental cues that are associated with food develop attractive and motivational properties that elicit reward-seeking behaviors in animals. However, when food-associated cues no longer lead to rewards, animals quickly adjust their behaviors by showing a transient increase of reward-seeking responses (invigoration) and a set of behavioral responses that resemble frustrative behaviors in humans. Repeated exposure to reward omission leads to behavioral attenuation that serves to suppress unproductive appetitive responses. Although significant progress has been made in elucidating the brain structures that regulate the acquisition and the extinction of reward-seeking responses, the neural circuits and brain mechanisms that control changes in behavioral responses during the initial phase of reward omission remain elusive. Emerging evidence suggests that neurons in the anterior portion of the paraventricular nucleus of the thalamus (aPVT) are activated by reward- associated cues and contribute to the regulation of emotional responses during unexpected omission of reward. Whereas activity in the aPVT to nucleus accumbens pathway decreases reward seeking, activity in the aPVT to central amygdala pathway increases it, suggesting that the aPVT is a potential candidate to regulate behavioral invigoration during reward omission. Here we propose to study how cortical and subcortical inputs to the aPVT regulate the dynamic activity of projection-defined aPVT neurons during reward omission. Using in vitro electrophysiology, we will study the intrinsic properties and synaptic dynamics of distinct aPVT neurons and their afferents. Using a food-seeking task in which rats are exposed to reward omission, we will investigate the neuronal activity patterns of aPVT neurons in vivo, and correlate their activity with the animal's behavior during the test. Subsequent gain-of-function and loss-of-function experiments will test the sufficiency and necessity of distinct aPVT afferents. These experiments will provide insights into the neural circuits that detect changes in reward availability and rapidly adjust animals' behavior during the initial phase of reward omission.