Project 1- Project 1: Defining the structure and function of NTS satiety circuits While much recent energy balance-directed research has focused upon hypothalamic circuits, these hypothalamic systems largely mediate their effects on feeding via hindbrain circuits. Furthermore, many of the most effective pharmacological obesity treatments act on brainstem satiety systems. The inadvertent production of aversive symptoms such as nausea, which is mediated by circuits that are intermingled with brainstem satiety systems, represents one of the most important limitations to therapies that target these systems, however. Thus, it will be crucial to distinguish the brainstem circuits that encode satiety from those that promote nausea and other aversive symptoms, since the non-aversive circuits represent ideal targets for therapy. This project will define the neural circuits by which the NTS controls feeding and by which it signals aversive or non-aversive responses, as appropriate for the stimulus. In addition to enhancing our understanding of neural systems important for the control of ingestive behavior, distinguishing non-aversive from aversive satiety systems may permit the design of improved therapies to decrease food intake and combat obesity.
This project will define the neural circuits by which the NTS integrates and transmits gut signals to control feeding with the appropriate valence for the stimulus. In addition to enhancing our understanding of neural systems important for the control of ingestive behavior, disentangling the neural systems that encode satiety and positive valence from those that mediate anorexia with negative valence may permit the design of improved therapies to decrease food intake and combat obesity.
