Identification of a Stress-Sensitive Anorexigenic Neurocircuit From Medial Prefrontal Cortex to Lateral Hypothalamus

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 -