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

Louisa E. Linders, Lefkothea Patrikiou, Mariano Soiza-Reilly, Evelien H. S. Schut, Bram F. Schaffelaar, Leonard Böger, Inge G. Wolterink-Donselaar, Mieneke C. M. Luijendijk, Roger A. H. Adan and Frank J. Meye ()
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Louisa E. Linders: Utrecht University
Lefkothea Patrikiou: Utrecht University
Mariano Soiza-Reilly: University of Buenos Aires
Evelien H. S. Schut: Utrecht University
Bram F. Schaffelaar: Utrecht University
Leonard Böger: Utrecht University
Inge G. Wolterink-Donselaar: Utrecht University
Mieneke C. M. Luijendijk: Utrecht University
Roger A. H. Adan: Utrecht University
Frank J. Meye: Utrecht University

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-34625-7

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