Feeding is a complex motivated behavior that is controlled not just by metabolic and homeostatic factors, but also by environmental factors such as emotion and the hedonic nature of the food itself. Yet, little is known about how brain regions involved in cognition and emotion might contribute to overeating, and therefore, obesity. We used a recently developed behavioral task in which learned contextual cues induce feeding even in sated mice to investigate the underlying neural mechanisms. Using viral tracing, molecular profiling and chemo/optogenetic techniques, we discovered that an insular cortex projection to the central amygdala is required for conditioned overconsumption but not homeostatic feeding. The projection neurons express nitric oxide synthase-1 and activation of this population suppresses satiety signals in the central amygdala. The data thus indicate that the insular cortex provides top down control of homeostatic circuits to promote overconsumption in response to learned cues.

A molecularly defined insular cortex --> central amygdala circuit mediates conditioned overconsumption of food.