Nutritional Regulation of Hunger Circuits in Awake, Behaving Mice

Abstract

Food intake is controlled by specialized neural circuits that monitor nutritional signals from the body, but how nutritional state is represented in the dynamics of these circuits is unknown. I will describe recent work from my lab investigating the dynamics of AgRP neurons, a key neural population that controls hunger. To understand how these cells are regulated by physiologic signals, we have developed a preparation that enables recording of AgRP neuron activity during intragastric feeding of awake, behaving mice. Using this approach, we have shown that AgRP neurons are rapidly inhibited by gastrointestinal nutrients on a timescale of minutes. This rapid feedback is proportional to the number of calories infused, independent of macronutrient identity, and mediated by a combination of hormonal signals. I will discuss general principles of gut-brain communication that have been suggested by these findings as well as key questions that remain to be answered.