Identification of a Stress-Sensitive Anorexigenic Neurocircuit From Medial Prefrontal Cortex to Lateral Hypothalamus
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Identification of a Stress-Sensitive Anorexigenic Neurocircuit From Medial Prefrontal Cortex to Lateral Hypothalamus. / Clarke, Rachel E; Voigt, Katharina; Reichenbach, Alex; Stark, Romana; Bharania, Urvi; Dempsey, Harry; Lockie, Sarah H; Mequinion, Mathieu; Lemus, Moyra; Wei, Bowen; Reed, Felicia; Rawlinson, Sasha; Nunez-Iglesias, Juan; Foldi, Claire J; Kravitz, Alexxai V; Verdejo-Garcia, Antonio; Andrews, Zane B.
In: BIOL PSYCHIAT, Vol. 93, No. 4, 15.02.2023, p. 309-321.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Identification of a Stress-Sensitive Anorexigenic Neurocircuit From Medial Prefrontal Cortex to Lateral Hypothalamus
AU - Clarke, Rachel E
AU - Voigt, Katharina
AU - Reichenbach, Alex
AU - Stark, Romana
AU - Bharania, Urvi
AU - Dempsey, Harry
AU - Lockie, Sarah H
AU - Mequinion, Mathieu
AU - Lemus, Moyra
AU - Wei, Bowen
AU - Reed, Felicia
AU - Rawlinson, Sasha
AU - Nunez-Iglesias, Juan
AU - Foldi, Claire J
AU - Kravitz, Alexxai V
AU - Verdejo-Garcia, Antonio
AU - Andrews, Zane B
N1 - Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
PY - 2023/2/15
Y1 - 2023/2/15
N2 - BACKGROUND: A greater understanding of how the brain controls appetite is fundamental to developing new approaches for treating diseases characterized by dysfunctional feeding behavior, such as obesity and anorexia nervosa.METHODS: By modeling neural network dynamics related to homeostatic state and body mass index, we identified a novel pathway projecting from the medial prefrontal cortex (mPFC) to the lateral hypothalamus (LH) in humans (n = 53). We then assessed the physiological role and dissected the function of this mPFC-LH circuit in mice.RESULTS: In vivo recordings of population calcium activity revealed that this glutamatergic mPFC-LH pathway is activated in response to acute stressors and inhibited during food consumption, suggesting a role in stress-related control over food intake. Consistent with this role, inhibition of this circuit increased feeding and sucrose seeking during mild stressors, but not under nonstressful conditions. Finally, chemogenetic or optogenetic activation of the mPFC-LH pathway is sufficient to suppress food intake and sucrose seeking in mice.CONCLUSIONS: These studies identify a glutamatergic mPFC-LH circuit as a novel stress-sensitive anorexigenic neural pathway involved in the cortical control of food intake.
AB - BACKGROUND: A greater understanding of how the brain controls appetite is fundamental to developing new approaches for treating diseases characterized by dysfunctional feeding behavior, such as obesity and anorexia nervosa.METHODS: By modeling neural network dynamics related to homeostatic state and body mass index, we identified a novel pathway projecting from the medial prefrontal cortex (mPFC) to the lateral hypothalamus (LH) in humans (n = 53). We then assessed the physiological role and dissected the function of this mPFC-LH circuit in mice.RESULTS: In vivo recordings of population calcium activity revealed that this glutamatergic mPFC-LH pathway is activated in response to acute stressors and inhibited during food consumption, suggesting a role in stress-related control over food intake. Consistent with this role, inhibition of this circuit increased feeding and sucrose seeking during mild stressors, but not under nonstressful conditions. Finally, chemogenetic or optogenetic activation of the mPFC-LH pathway is sufficient to suppress food intake and sucrose seeking in mice.CONCLUSIONS: These studies identify a glutamatergic mPFC-LH circuit as a novel stress-sensitive anorexigenic neural pathway involved in the cortical control of food intake.
KW - Animals
KW - Humans
KW - Mice
KW - Feeding Behavior/physiology
KW - Hypothalamic Area, Lateral/physiology
KW - Prefrontal Cortex/physiology
KW - Stress, Psychological/physiopathology
U2 - 10.1016/j.biopsych.2022.08.022
DO - 10.1016/j.biopsych.2022.08.022
M3 - SCORING: Journal article
C2 - 36400605
VL - 93
SP - 309
EP - 321
JO - BIOL PSYCHIAT
JF - BIOL PSYCHIAT
SN - 0006-3223
IS - 4
ER -