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.