The hindbrain‐hypothalamic noradrenergic pathway controls homeostatic food intake but not cue‐induced appetitive behaviors

Abstract Nucleus of the solitary tract (NTS) A2 noradrenergic neurons are critical in regulating food intake. In addition to their well‐established role in homeostatic feeding, there is also evidence indicating their contribution in non‐homeostatic feeding behaviors. However, whether their control of homeostatic and non‐homeostatic feeding behaviors is mediated via shared or separate neural circuits is not well understood. Given that NTS A2 neurons project to the lateral hypothalamus (LH), a brain region implicated in both homeostatic and non‐homeostatic feeding, this study examined whether NTS A2 neurons project to LH (A2 NTS→LH ) to control these feeding behaviors. We used chemogenetics to activate A2 NTS→LH neurons. To assess homeostatic feeding, we measured chow intake in the home cage for 24 h and to assess non‐homeostatic feeding, we used the Pavlovian appetitive conditioning task to measure cue‐induced appetitive behavior. Using anatomical tracing, we first showed that ~20% of NTS A2 neurons project to the LH and these LH‐projecting NTS A2 neurons are activated by food intake. Chemogenetic activation of A2 NTS→LH neurons significantly suppressed home cage chow intake and body weight. However, while activation of all NTS A2 neurons suppressed cue‐induced appetitive behavior, pathway specific stimulation of A2 NTS→LH neurons did not affect this cue‐driven behavior. Together, these results indicate that the A2 NTS→LH neurons are involved in the control of homeostatic food intake but not cue‐induced appetitive behaviors, and suggest the contribution of distinct NTS A2 pathways and LH neurons in the regulation of homeostatic and non‐homeostatic feeding behaviors.