Role of the parasubthalamic nucleus (PSTN) in the central regulation of feeding behavior

PROJECT SUMMARY The motivation to eat depends on the relative balance of activity between orexigenic (appetite inducing) and anorexigenic (appetite suppressing) brain systems. An abnormal balance of activity in these systems can lead to substantial health problems with high associated economic costs. In the United States, over half the population is considered overweight, and the aggregate economic cost is estimated in excess of $60 billion per year. Undernourishment is also a substantial problem: abnormal appetite suppression, as can occur during infection, old age, and cancer, can lead to severely low body weight and malnutrition. However, despite obvious importance, the neural basis of hunger and appetite suppression continues to be poorly understood at a neuronal or circuit level, and is currently an important focus of investigation. In recent years, the parasubthalamic nucleus (PSTN), a relatively understudied population of neurons in the posterolateral hypothalamus, has been recognized as playing an important role in the regulation of appetite suppression. However, several important questions about the PSTN remain. The purpose of this proposal is to study the afferent connectivity, activity patterns, and necessity of individual PSTN subpopulations in mediating appetite suppression. In Specific Aim 1, we will determine the sources of incoming, afferent projections to individual PSTN subpopulations. In Specific Aim 2, we will study whether orexigenic stimuli and anorexigenic stimuli have opposing effects on PSTN neuronal activity. In Specific Aim 3, we will test the necessity of individual PSTN subpopulations for the appetite suppression observed following a large meal and in response to appetite-suppressing hormones. We will also study the necessity of PSTN neurons that project to specific, downstream targets in the brain in mediating the effects of appetite-suppressing hormones. Taken together, the experiments in this proposal will allow for continued understanding of the role of the PSTN in the central regulation of feeding behavior.