TY - JOUR
T1 - Stress-driven potentiation of lateral hypothalamic synapses onto ventral tegmental area dopamine neurons causes increased consumption of palatable food
AU - Linders, Louisa E.
AU - Patrikiou, Lefkothea
AU - Soiza-Reilly, Mariano
AU - Schut, Evelien H.S.
AU - van Schaffelaar, Bram F.
AU - Böger, Leonard
AU - Wolterink-Donselaar, Inge G.
AU - Luijendijk, Mieneke C.M.
AU - Adan, Roger A.H.
AU - Meye, Frank J.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85141695961&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-34625-7
DO - 10.1038/s41467-022-34625-7
M3 - Article
C2 - 36371405
AN - SCOPUS:85141695961
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 6898
ER -