Stress-driven potentiation of lateral hypothalamic synapses onto ventral tegmental area dopamine neurons causes increased consumption of palatable food

Stress can cause overconsumption of palatable high caloric food. Despite the important role of stress eating in obesity and (binge) eating disorders, its underlying neural mechanisms remain unclear. Here we demonstrate in mice that stress alters lateral hypothalamic area (LHA) control over the ventr...

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Bibliographic Details
Published in:	Nature communications Vol. 13; no. 1; p. 6898
Main Authors:	Linders, Louisa E., Patrikiou, Lefkothea, Soiza-Reilly, Mariano, Schut, Evelien H. S., van Schaffelaar, Bram F., Böger, Leonard, Wolterink-Donselaar, Inge G., Luijendijk, Mieneke C. M., Adan, Roger A. H., Meye, Frank J.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 12-11-2022 Nature Publishing Group Nature Portfolio
Subjects:	631/378/2591 631/378/3920 64/60 9/10 9/74 96 Adaptation Animals Circuits Dopamine Dopaminergic Neurons Eating disorders Food Food consumption Glutamatergic transmission Humanities and Social Sciences Hypothalamic Area, Lateral Hypothalamus Hypothalamus (lateral) Mice multidisciplinary Neurons Obesity Potentiation Prefrontal cortex Receptors, AMPA Reinforcement Science Science (multidisciplinary) Social interactions Stress Synapses Ventral Tegmental Area Ventral tegmentum α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors
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Summary:	Stress can cause overconsumption of palatable high caloric food. Despite the important role of stress eating in obesity and (binge) eating disorders, its underlying neural mechanisms remain unclear. Here we demonstrate in mice that stress alters lateral hypothalamic area (LHA) control over the ventral tegmental area (VTA), thereby promoting overconsumption of palatable food. Specifically, we show that glutamatergic LHA neurons projecting to the VTA are activated by social stress, after which their synapses onto dopamine neurons are potentiated via AMPA receptor subunit alterations. We find that stress-driven strengthening of these specific synapses increases LHA control over dopamine output in key target areas like the prefrontal cortex. Finally, we demonstrate that while inducing LHA-VTA glutamatergic potentiation increases palatable fat intake, reducing stress-driven potentiation of this connection prevents such stress eating. Overall, this study provides insights in the neural circuit adaptations caused by stress that drive overconsumption of palatable food. Stress can increase the consumption of rewarding food, which contributes to obesity and binge eating disorders. Here the authors show that stress eating depends on a strengthened connection between the lateral hypothalamus and the dopamine system.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-022-34625-7