Journal
JOURNAL OF NEUROSCIENCE
Volume 37, Issue 25, Pages 6053-6065Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0155-17.2017
Keywords
compulsivity; DREADD; energy expenditure; feeding; locomotor activity; marble-burying test
Categories
Funding
- American Heart Association Grant [AHA053298N]
- National Institutes of Health (NIH) [P/F DK020572-30, R01-DK092587, P20-GM103528, T32-DK064584]
- Centers of Biomedical Research Excellence (NIH) from the NIH [P20-GM103528]
- Clinical Nutritional Research Unit (NIH) from the NIH [1P30-DK072476]
- Animal Phenotyping Core through National Institute of Diabetes and Digestive and Kidney Diseases Nutritional Obesity Research Centers Grant (Nutritional Programming: Environmental and Molecular Interactions) at the Pennington Biomedical Research Center [2P30 DK072476]
- NIH [R01-DK047348]
- [R01-DK105032]
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The lateral hypothalamus (LHA) integrates reward and appetitive behavior and is composed of many overlapping neuronal populations. Recent studies associated LHA GABAergic neurons (LHA(GABA)), which densely innervate the ventral tegmental area (VTA), with modulation of food reward and consumption; yet, LHA(GABA) projections to the VTA exclusively modulated food consumption, not reward. We identified a subpopulation of LHA(GABA) neurons that coexpress the neuropeptide galanin (LHA(Gal)). These LHA(Gal) neurons also modulate food reward, but lack direct VTA innervation. We hypothesized that LHA(Gal) neurons may represent a subpopulation of LHA(GABA) neurons that mediates food reward independent of direct VTA innervation. We used chemogenetic activation of LHA(Gal) or LHA(GABA) 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(Gal) or LHA(GABA) neuronal activation both increased operant food- seeking behavior, but only activation of LHA(GABA) neurons increased overall chow consumption. Additionally, LHA(Gal) or LHA(GABA) neuronal activation similarly induced locomotor activity, but with striking differences in modality. Activation of LHA(GABA) neurons induced compulsive-like locomotor behavior; while LHA(Gal) neurons induced locomotor activity without compulsivity. Thus, LHA(Ga)l neurons define a subpopulation of LHA(GABA) 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.
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