Orexigenic AgRP neurons in the brainstem

Project Summary/Abstract Prevalence of obesity is at an all-time high, but treatment methods are still limited. Proper regulation of food intake and body weight rely on coordinated control of orexigenic and anorexigenic neurons in the central nervous system, but our understanding of the neuronal circuits governing feeding is still not complete. Agouti- related protein (AgRP)-expressing neurons are known to be one of the most potent drivers of feeding, and they are currently thought to be exclusively located in the mediobasal hypothalamus. In this application, we present evidence demonstrating the existence of a previously unknown population of AgRP-expressing cells in the area postrema, adjacent subpostrema area and the commissural part of the nucleus of the solitary tract. We further show that these hindbrain AgRP cells potently promote feeding. In this study, we will identify neural substrates that mediate the orexigenic effects of hindbrain AgRP neurons. We will determine how these neurons are regulated by metabolic signals and explore functional redundancy between hindbrain and hypothalamic AgRP neurons. Together, experiments outlined in this proposal will delineate the mechanisms underlying the orexigenic effects of this novel population of AgRP neurons in the brainstem. As such, this study will broaden our knowledge on how central neuronal network operates to control feeding.