A rapidly acting glutamatergic ARC→PVH satiety circuit postsynaptically regulated by α-MSH

Henning Fenselau; John N Campbell; Anne M J Verstegen; Joseph C Madara; Jie Xu; Bhavik P Shah; Jon M Resch; Zongfang Yang; Yael Mandelblat-Cerf; Yoav Livneh; Bradford B Lowell

doi:10.1038/nn.4442

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A rapidly acting glutamatergic ARC→PVH satiety circuit postsynaptically regulated by α-MSH

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A rapidly acting glutamatergic ARC→PVH satiety circuit postsynaptically regulated by α-MSH

Henning Fenselau, John N Campbell, Anne M J Verstegen, Joseph C Madara, Jie Xu, Bhavik P Shah, Jon M Resch, Zongfang Yang, Yael Mandelblat-Cerf, Yoav Livneh, …

Nature neuroscience, Vol.20(1), pp.42-51

01/2017

DOI: 10.1038/nn.4442

PMCID: PMC5191921

PMID: 27869800

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http://nrs.harvard.edu/urn-3:HUL.InstRepos:33029878View

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Abstract

Arcuate nucleus (ARC) neurons sense the fed or fasted state and regulate hunger. Agouti-related protein (AgRP) neurons in the ARC (ARC neurons) are stimulated by fasting and, once activated, they rapidly (within minutes) drive hunger. Pro-opiomelanocortin (ARC ) neurons are viewed as the counterpoint to ARC neurons. They are regulated in an opposite fashion and decrease hunger. However, unlike ARC neurons, ARC neurons are extremely slow in affecting hunger (many hours). Thus, a temporally analogous, rapid ARC satiety pathway does not exist or is presently unidentified. Here we show that glutamate-releasing ARC neurons expressing oxytocin receptor, unlike ARC neurons, rapidly cause satiety when chemo- or optogenetically manipulated. These glutamatergic ARC projections synaptically converge with GABAergic ARC projections on melanocortin-4 receptor (MC4R)-expressing satiety neurons in the paraventricular hypothalamus (PVH neurons). Transmission across the ARC →PVH synapse is potentiated by the ARC neuron-derived MC4R agonist, α-melanocyte stimulating hormone (α-MSH). This excitatory ARC→PVH satiety circuit, and its modulation by α-MSH, provides insight into regulation of hunger and satiety.

Pro-Opiomelanocortin - metabolism

Synaptic Potentials - physiology

Animals

Hypothalamus - metabolism

Arcuate Nucleus of Hypothalamus - metabolism

Mice, Transgenic

Neurons - metabolism

Energy Metabolism - physiology

Hunger - physiology

Nerve Net - physiology

alpha-MSH - metabolism

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Title: Subtitle: A rapidly acting glutamatergic ARC→PVH satiety circuit postsynaptically regulated by α-MSH
Creators: Henning Fenselau - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
John N Campbell - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Anne M J Verstegen - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Joseph C Madara - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Jie Xu - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Bhavik P Shah - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Jon M Resch - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Zongfang Yang - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Yael Mandelblat-Cerf - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Yoav Livneh - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Bradford B Lowell - Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA
Resource Type: Journal article
Publication Details: Nature neuroscience, Vol.20(1), pp.42-51
DOI: 10.1038/nn.4442
PMID: 27869800
PMCID: PMC5191921
NLM abbreviation: Nat Neurosci
ISSN: 1097-6256
eISSN: 1546-1726
Publisher: United States
Grant note: R37 DK053477 / NIDDK NIH HHS R01 DK096010 / NIDDK NIH HHS R01 DK111401 / NIDDK NIH HHS R01 DK089044 / NIDDK NIH HHS DP2 DK105570 / NIDDK NIH HHS R01 DK075632 / NIDDK NIH HHS F32 DK103387 / NIDDK NIH HHS P30 DK046200 / NIDDK NIH HHS P30 DK057521 / NIDDK NIH HHS
Language: English
Date published: 01/2017
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984065853702771

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A rapidly acting glutamatergic ARC→PVH satiety circuit postsynaptically regulated by α-MSH

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