Galanin-Expressing GABA Neurons in the Lateral Hypothalamus Modulate Food Reward and Noncompulsive Locomotion.

The lateral hypothalamus (LHA) integrates reward and appetitive behavior and is composed of many overlapping neuronal populations. Recent studies associated LHA GABAergic neurons (LHA ), which densely innervate the ventral tegmental area (VTA), with modulation of food reward and consumption; yet, LHA projections to the VTA exclusively modulated food consumption, not reward. We identified a subpopulation of LHA neurons that coexpress the neuropeptide galanin (LHA ). These LHA neurons also modulate food reward, but lack direct VTA innervation. We hypothesized that LHA neurons may represent a subpopulation of LHA neurons that mediates food reward independent of direct VTA innervation. We used chemogenetic activation of LHA or LHA neurons in mice to compare their role in feeding behavior. We further analyzed locomotor behavior to understand how differential VTA connectivity and transmitter release in these LHA neurons influences this behavior. LHA or LHA neuronal activation both increased operant food-seeking behavior, but only activation of LHA neurons increased overall chow consumption. Additionally, LHA or LHA neuronal activation similarly induced locomotor activity, but with striking differences in modality. Activation of LHA neurons induced compulsive-like locomotor behavior; while LHA neurons induced locomotor activity without compulsivity. Thus, LHA neurons define a subpopulation of LHA neurons without direct VTA innervation that mediate noncompulsive food-seeking behavior. We speculate that the striking difference in compulsive-like locomotor behavior is also based on differential VTA innervation. The downstream neural network responsible for this behavior and a potential role for galanin as neuromodulator remains to be identified. The lateral hypothalamus (LHA) regulates motivated feeding behavior via GABAergic LHA neurons. The molecular identity of LHA neurons is heterogeneous and largely undefined. Here we introduce LHA neurons as a subset of LHA neurons that lack direct innervation of the ventral tegmental area (VTA). LHA neurons are sufficient to drive motivated feeding and locomotor activity similar to LHA neurons, but without inducing compulsive-like behaviors, which we propose to require direct VTA innervation. Our study integrates galanin-expressing LHA neurons into our current understanding of the neuronal circuits and molecular mechanisms of the LHA that contribute to motivated feeding behaviors.