The Inhibitory Circuit Architecture of the Lateral Hypothalamus Orchestrates Feeding

TLDR

The growing prevalence of overeating disorders contributes to the obesity epidemic, and dysfunction of specific neural circuits—especially in the lateral hypothalamus—may underlie maladaptive feeding behaviors. Inhibitory inputs from the extended amygdala suppress lateral hypothalamic glutamatergic neurons, thereby controlling food intake and demonstrating how dysregulation at distinct nodes can cascade into maladaptive feeding.

Abstract

The growing prevalence of overeating disorders is a key contributor to the worldwide obesity epidemic. Dysfunction of particular neural circuits may trigger deviations from adaptive feeding behaviors. The lateral hypothalamus (LH) is a crucial neural substrate for motivated behavior, including feeding, but the precise functional neurocircuitry that controls LH neuronal activity to engage feeding has not been defined. We observed that inhibitory synaptic inputs from the extended amygdala preferentially innervate and suppress the activity of LH glutamatergic neurons to control food intake. These findings help explain how dysregulated activity at a number of unique nodes can result in a cascading failure within a defined brain network to produce maladaptive feeding.