Energy state guides reward seeking via an extended amygdala to lateral hypothalamus pathway

Impaired regulation of food intake underlies numerous health problems, including obesity and type 2 diabetes, yet how brain systems controlling reward seeking become dysregulated to promote overeating is unknown. Glutamatergic neurons of the lateral hypothalamic area (LHA) are thought to act as a brake on feeding, which is dysregulated during diet-induced obesity. These neurons receive input from the extended amygdala, including the bed nucleus of the stria terminalis (BNST). However, the circuit mechanisms underlying the ability of this pathway to control feeding behavior and how they contribute to dysregulated eating are unclear. Here, we discover that the BNST→LHA pathway promotes reward seeking in an energy state-dependent manner by combining optogenetics, in vivo multiphoton calcium imaging, and electrophysiology. Synaptic strength and neuronal function within the BNST→LHA pathway are dynamically regulated according to energy state to guide reward seeking. These findings suggest that humoral factors modulate the function of the BNST→LHA pathway to align food seeking with current energy needs.