Collateralizing ventral subiculum melanocortin 4 receptor circuits regulate energy balance and food motivation

Uday Singh; Kenji Saito; Michael Z Khan; Jingwei Jiang; Brandon A Toth; Samuel R Rodeghiero; Jacob E Dickey; Yue Deng; Guorui Deng; Young-Cho Kim; Huxing Cui

doi:10.1016/j.physbeh.2023.114105

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Collateralizing ventral subiculum melanocortin 4 receptor circuits regulate energy balance and food motivation

Journal article

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Collateralizing ventral subiculum melanocortin 4 receptor circuits regulate energy balance and food motivation

Uday Singh, Kenji Saito, Michael Z Khan, Jingwei Jiang, Brandon A Toth, Samuel R Rodeghiero, Jacob E Dickey, Yue Deng, Guorui Deng, Young-Cho Kim, …

Physiology & behavior, Vol.262, 114105

01/31/2023

DOI: 10.1016/j.physbeh.2023.114105

PMCID: PMC9981473

PMID: 36736416

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Abstract

Hippocampal dysfunction is associated with major depressive disorder, a serious mental illness characterized by not only depressed mood but also appetite disturbance and dysregulated body weight. However, the underlying mechanisms by which hippocampal circuits regulate metabolic homeostasis remain incompletely understood. Here we show that collateralizing melanocortin 4 receptor (MC4R) circuits in the ventral subiculum (vSUB), one of the major output structures of the hippocampal formation, affect food motivation and energy balance. Viral-mediated cell type- and projection-specific input-output circuit mapping revealed that the nucleus accumbens shell (NAcSh)-projecting vSUB neurons send extensive collateral projections of to various hypothalamic nuclei known to be important for energy balance, including the arcuate, ventromedial and dorsomedial nuclei, and receive monosynaptic inputs mainly from the ventral CA1 and the anterior paraventricular nucleus of thalamus. Chemogenetic activation of NAcSh-projecting vSUB neurons lead to increase in motivation to obtain palatable food without noticeable effect on homeostatic feeding. Viral-mediated restoration of MC4R signaling in the vSUB partially restores obesity in MC4R-null mice without affecting anxiety- and depression-like behaviors. Collectively, these results delineate vSUB circuits to the unprecedented level of precision and identify the vSUB signaling as a novel regulator of food reward and energy balance.

melanocortin 4 receptor

ventral subiculum

major depressive disorder

food motivation

nucleus accumbens

energy homeostasis

Details

Title: Subtitle: Collateralizing ventral subiculum melanocortin 4 receptor circuits regulate energy balance and food motivation
Creators: Uday Singh - University of Iowa
Kenji Saito - University of Iowa
Michael Z Khan - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, United States
Jingwei Jiang - University of Iowa
Brandon A Toth - University of Iowa
Samuel R Rodeghiero - University of Iowa
Jacob E Dickey - University of Iowa
Yue Deng - University of Iowa
Guorui Deng - University of Iowa
Young-Cho Kim - Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA, United States
Huxing Cui
Resource Type: Journal article
Publication Details: Physiology & behavior, Vol.262, 114105
DOI: 10.1016/j.physbeh.2023.114105
PMID: 36736416
PMCID: PMC9981473
NLM abbreviation: Physiol Behav
ISSN: 0031-9384
eISSN: 1873-507X
Grant note: DOI: 10.13039/100000968, name: American Heart Association, award: 14SDG20140054; DOI: 10.13039/100000002, name: National Institutes of Health, award: HL127673, HL153274, MH109920
Language: English
Date published: 01/31/2023
Academic Unit: Neurology; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9984363682802771

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