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

Animals Humans Mice Feeding Behavior / physiology Hypothalamic Area, Lateral / physiology Prefrontal Cortex / physiology Stress, Psychological / physiopathology
Calcium imaging Chemogenetics FED3 Feeding behavior Network modeling Optogenetics

Journal

Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264

Informations de publication

Date de publication:
15 02 2023
Historique:
received: 16 01 2022
revised: 04 08 2022
accepted: 04 08 2022
pubmed: 19 11 2022
medline: 21 1 2023
entrez: 18 11 2022
Statut: ppublish

Résumé

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. 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. 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. These studies identify a glutamatergic mPFC-LH circuit as a novel stress-sensitive anorexigenic neural pathway involved in the cortical control of food intake.

Sections du résumé

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.

Identifiants

DOI: 10.1016/j.biopsych.2022.08.022 PMID: 36400605
pubmed: 36400605
pii: S0006-3223(22)01550-5
doi: 10.1016/j.biopsych.2022.08.022
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

309-321

Informations de copyright

Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Auteurs

Rachel E Clarke (RE)

Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Victoria, Australia.

Katharina Voigt (K)

Turner Institute for Brain and Mental Health, Monash University, Clayton, Victoria, Australia.

Alex Reichenbach (A)

Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Victoria, Australia.

Romana Stark (R)

Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Victoria, Australia.

Urvi Bharania (U)

Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Victoria, Australia.

Harry Dempsey (H)

Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Victoria, Australia.

Sarah H Lockie (SH)

Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Victoria, Australia.

Mathieu Mequinion (M)

Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Victoria, Australia.

Moyra Lemus (M)

Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Victoria, Australia.

Bowen Wei (B)

Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Victoria, Australia.

Felicia Reed (F)

Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Victoria, Australia.

Sasha Rawlinson (S)

Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Victoria, Australia.

Juan Nunez-Iglesias (J)

Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.

Claire J Foldi (CJ)

Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Victoria, Australia.

Alexxai V Kravitz (AV)

Departments of Psychiatry, Anesthesiology, and Neuroscience, Washington University in St. Louis, St. Louis, Missouri.

Antonio Verdejo-Garcia (A)

Turner Institute for Brain and Mental Health, Monash University, Clayton, Victoria, Australia.

Zane B Andrews (ZB)

Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Victoria, Australia. Electronic address: Zane.Andrews@monash.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Identification of a Stress-Sensitive...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Identification of a Stress-Sensitive...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Identification of a Stress-Sensitive...
questionsmedicales.fr › Phénomènes physiologiques › Alimentation et nutrition › Phénomènes physiologiques nutritionnels › Comportement alimentaire › Identification of a Stress-Sensitive...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Diencéphale › Hypothalamus › Aire hypothalamique latérale › Identification of a Stress-Sensitive...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Cortex cérébral › Lobe frontal › Cortex préfrontal › Identification of a Stress-Sensitive...
questionsmedicales.fr › Phénomènes psychologiques › Stress psychologique › Identification of a Stress-Sensitive...