Among the many complications of Prader-Willi Syndrome (PWS), the increased food intake (hyperphagia) has serious long-term medical consequences. The goal of this proposal is to define novel brain regions that may contribute to this problem. Studies of brain activity suggest that the prefrontal cortex might be different in PWS patients. This is an excellent candidate region for study in animal models, where we can define brain circuits that influence behavior. My lab studies food intake from a model of drug addiction whereby we attempt to find brain centers that motivate and/or regulate intake. We have obtained exciting data that connects the prefrontal cortex to food intake and the motivation to eat. In this proposal, we will test the role of the neural circuit in mediating and driving the hyperphagia in mouse models of PWS. This research is critical for us to fill the gap between human studies, that emphasize the cortex, and mouse work, which focuses on other brain regions. We anticipate that this work will be a first step in an important line of animal research that will incorporate this critical brain region into our neural models of PWS. This work will also set the stage for understanding how cortically-targeted therapeutics might benefit patients suffering from PWS.