The hindbrain-hypothalamic noradrenergic pathway controls homeostatic food intake but not cue-induced appetitive...

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.