© 2017 the authors. The lateral hypothalamus (LHA) integrates reward and appetitive behavior and is composed of many overlapping neuronal populations. Recent studies associated LHA GABAergic neurons (LHAGABA), which densely innervate the ventral tegmental area (VTA), with modulation of food reward and consumption; yet, LHAGABA projections to the VTA exclusively modulated food consumption, not reward. We identified a subpopulation of LHA GABA neurons that coexpress the neuropeptide galanin (LHAGal). TheseLHAGal neurons also modulate food reward, but lack direct VTA innervation. We hypothesized that LHAGal neurons may represent a subpopulation of LHAGABA neurons that mediates food reward independent of direct VTA innervation. We used chemogenetic activation of LHAGal or LHAGABA neurons in mice to compare their role in feeding behavior. We further analyzed locomotor behavior to understand how differentia lVTA connectivity and transmitter release in these LHA neurons influences this behavior. LHAGal or LHAGABA neuronal activation both increased operant food-seeking behavior, but only activation of LHAGABA neurons increased overall chow consumption. Additionally, LHAGal or LHAGABA neuronal activation similarly induced locomotor activity, but with striking differences in modality. Activation of LHAGABA neurons induced compulsive-like locomotor behavior; while LHAGal neurons induced locomotor activity without compulsivity. Thus, LHAGal neurons define a subpopulation of LHAGABA neurons without direct VTA innervation that mediate non compulsive 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.
Publication Source (Journal or Book title)
Journal of Neuroscience
Qualls-Creekmore, E., Yu, S., Francois, M., Hoang, J., Huesing, C., Bruce-Keller, A., Burk, D., Berthoud, H., Morrison, C., & Münzberg, H. (2017). Galanin-expressing GABA neurons in the lateral hypothalamus modulate food reward and noncompulsive locomotion. Journal of Neuroscience, 37 (25), 6053-6065. https://doi.org/10.1523/JNEUROSCI.0155-17.2017