Neuroanatomy of melanocortin-4 receptor pathway in the lateral hypothalamic area

Huxing Cui; Jong-Woo Sohn; Laurent Gautron; Hisayuki Funahashi; Kevin W Williams; Joel K Elmquist; Michael Lutter

doi:10.1002/cne.23145

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Neuroanatomy of melanocortin-4 receptor pathway in the lateral hypothalamic area

Journal article

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Neuroanatomy of melanocortin-4 receptor pathway in the lateral hypothalamic area

Huxing Cui, Jong-Woo Sohn, Laurent Gautron, Hisayuki Funahashi, Kevin W Williams, Joel K Elmquist and Michael Lutter

Journal of comparative neurology (1911), Vol.520(18), pp.4168-4183

12/15/2012

DOI: 10.1002/cne.23145

PMCID: PMC3652326

PMID: 22605619

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Abstract

The central melanocortin system regulates body energy homeostasis including the melanocortin-4 receptor (MC4R). The lateral hypothalamic area (LHA) receives dense melanocortinergic inputs from the arcuate nucleus of hypothalamus and regulates multiple processes including food intake, reward behaviors and autonomic function. Using a mouse line in which green fluorescent protein (GFP) is expressed under control of MC4R gene promoter, we systemically investigated MC4R signaling in the LHA by combining double immunohistochemistry, electrophysiology and retrograde tracing techniques. We found that LHA MC4R-GFP neurons co-express neurotensin as well as the leptin receptor but not with other peptide neurotransmitters found in the LHA including orexin, melanin concentrating hormone and nesfatin-1. Furthermore, electrophysiological recording demonstrated that leptin, but not the MC4R agonist melanotan II, hyperpolarizes the majority of LHA MC4R-GFP neurons in an ATP-sensitive potassium channel-dependent manner. Retrograde tracing revealed that LHA MC4R-GFP neurons do not project to the ventral tegmental area, dorsal raphe nucleus, nucleus accumbens and spinal cord, and only limited number of neurons project to the nucleus of solitary tract and parabrachial nucleus. Our findings provide new insight into MC4R signaling in the LHA and its potential implication in homeostatic regulation of body energy balance.

electrophyiosology

neurotensin

melanin concentrating hormone

orexin

Leptin receptor

nesfatin

Details

Title: Subtitle: Neuroanatomy of melanocortin-4 receptor pathway in the lateral hypothalamic area
Creators: Huxing Cui - Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas, 75390-9127
Jong-Woo Sohn - Departments of Internal Medicine and Pharmacology, Division of Hypothalamic Research, The University of Texas Southwestern Medical Center, Dallas, Texas, 75390-9127
Laurent Gautron - Departments of Internal Medicine and Pharmacology, Division of Hypothalamic Research, The University of Texas Southwestern Medical Center, Dallas, Texas, 75390-9127
Hisayuki Funahashi - Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555 Japan
Kevin W Williams - Departments of Internal Medicine and Pharmacology, Division of Hypothalamic Research, The University of Texas Southwestern Medical Center, Dallas, Texas, 75390-9127
Joel K Elmquist - Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas, 75390-9127
Michael Lutter - Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas, 75390-9127
Resource Type: Journal article
Publication Details: Journal of comparative neurology (1911), Vol.520(18), pp.4168-4183
DOI: 10.1002/cne.23145
PMID: 22605619
PMCID: PMC3652326
NLM abbreviation: J Comp Neurol
ISSN: 0021-9967
eISSN: 1096-9861
Grant note: K08 MH084058 || MH / National Institute of Mental Health : NIMH
Language: English
Date published: 12/15/2012
Academic Unit: Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9984040360402771

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