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

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

Research output: Contribution to journal › Article › peer-review

Abstract

Arcuate nucleus (ARC) neurons sense the fed or fasted state and regulate hunger. Agouti-related protein (AgRP) neurons in the ARC (ARC^AgRP neurons) are stimulated by fasting and, once activated, they rapidly (within minutes) drive hunger. Pro-opiomelanocortin (ARC^POMC) neurons are viewed as the counterpoint to ARC^AgRP neurons. They are regulated in an opposite fashion and decrease hunger. However, unlike ARC^AgRP neurons, ARC^POMC 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^POMC neurons, rapidly cause satiety when chemo- or optogenetically manipulated. These glutamatergic ARC projections synaptically converge with GABAergic ARC^AgRP projections on melanocortin-4 receptor (MC4R)-expressing satiety neurons in the paraventricular hypothalamus (PVH MC4R neurons). Transmission across the ARC Glutamatergic →PVH MC4R synapse is potentiated by the ARC^POMC 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.

Original language	English
Pages (from-to)	42-51
Number of pages	10
Journal	Nature Neuroscience
Volume	20
Issue number	1
Early online date	21 Nov 2016
DOIs	https://doi.org/10.1038/nn.4442
State	Published - 1 Jan 2017
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Neuroscience

Access to Document

10.1038/nn.4442

http://europepmc.org/article/PMC/5191921License: Unspecified

Cite this

@article{cdfde1f3c15d45ea8af47ddac37cff8d,

title = "A rapidly acting glutamatergic ARC→PVH satiety circuit postsynaptically regulated by α-MSH",

abstract = "Arcuate nucleus (ARC) neurons sense the fed or fasted state and regulate hunger. Agouti-related protein (AgRP) neurons in the ARC (ARCAgRP neurons) are stimulated by fasting and, once activated, they rapidly (within minutes) drive hunger. Pro-opiomelanocortin (ARCPOMC) neurons are viewed as the counterpoint to ARCAgRP neurons. They are regulated in an opposite fashion and decrease hunger. However, unlike ARCAgRP neurons, ARCPOMC 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 ARCPOMC neurons, rapidly cause satiety when chemo- or optogenetically manipulated. These glutamatergic ARC projections synaptically converge with GABAergic ARCAgRP projections on melanocortin-4 receptor (MC4R)-expressing satiety neurons in the paraventricular hypothalamus (PVH MC4R neurons). Transmission across the ARC Glutamatergic →PVH MC4R synapse is potentiated by the ARCPOMC 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.",

author = "Henning Fenselau and Campbell, \{John N.\} and Verstegen, \{Anne M.J.\} and Madara, \{Joseph C.\} and Jie Xu and Shah, \{Bhavik P.\} and Resch, \{Jon M.\} and Zongfang Yang and Yael Mandelblat-Cerf and Yoav Livneh and Lowell, \{Bradford B.\}",

note = "We thank members of B.B.L.'s laboratory for discussions. This research was funded by the following NIH grants to B.B.L.: R01 DK075632, R01 DK096010, R01 DK089044, R01 DK111401, P30 DK046200, P30 DK057521; to J.M.R.: F32 DK103387; to J.N.C.: AHA Postdoctoral Fellowship 14POST20100011. Y.M.-C. was supported by a Charles A. King postdoctoral fellowship. Y.L. was supported by an EMBO postdoctoral fellowship. Contributions - H.F. and B.B.L. designed the experiments and analyzed data. J.N.C. performed the single-cell RNA-seq experiments with help from Y.M.-C. H.F. and A.M.J.V. conducted the behavioral and histological studies with help from J.M.R. and Z.Y. H.F. performed the electrophysiological experiments with help from J.C.M. and Y.L. J.X. generated Pomc-IRES-cre mice. B.P.S. generated PomcloxP mice. H.F. and B.B.L. wrote the manuscript with comments from all of the authors.",

year = "2017",

month = jan,

day = "1",

doi = "10.1038/nn.4442",

language = "الإنجليزيّة",

volume = "20",

pages = "42--51",

journal = "Nature Neuroscience",

issn = "1097-6256",

publisher = "Nature Research",

number = "1",

}

TY - JOUR

T1 - A rapidly acting glutamatergic ARC→PVH satiety circuit postsynaptically regulated by α-MSH

AU - Fenselau, Henning

AU - Campbell, John N.

AU - Verstegen, Anne M.J.

AU - Madara, Joseph C.

AU - Xu, Jie

AU - Shah, Bhavik P.

AU - Resch, Jon M.

AU - Yang, Zongfang

AU - Mandelblat-Cerf, Yael

AU - Livneh, Yoav

AU - Lowell, Bradford B.

N1 - We thank members of B.B.L.'s laboratory for discussions. This research was funded by the following NIH grants to B.B.L.: R01 DK075632, R01 DK096010, R01 DK089044, R01 DK111401, P30 DK046200, P30 DK057521; to J.M.R.: F32 DK103387; to J.N.C.: AHA Postdoctoral Fellowship 14POST20100011. Y.M.-C. was supported by a Charles A. King postdoctoral fellowship. Y.L. was supported by an EMBO postdoctoral fellowship. Contributions - H.F. and B.B.L. designed the experiments and analyzed data. J.N.C. performed the single-cell RNA-seq experiments with help from Y.M.-C. H.F. and A.M.J.V. conducted the behavioral and histological studies with help from J.M.R. and Z.Y. H.F. performed the electrophysiological experiments with help from J.C.M. and Y.L. J.X. generated Pomc-IRES-cre mice. B.P.S. generated PomcloxP mice. H.F. and B.B.L. wrote the manuscript with comments from all of the authors.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Arcuate nucleus (ARC) neurons sense the fed or fasted state and regulate hunger. Agouti-related protein (AgRP) neurons in the ARC (ARCAgRP neurons) are stimulated by fasting and, once activated, they rapidly (within minutes) drive hunger. Pro-opiomelanocortin (ARCPOMC) neurons are viewed as the counterpoint to ARCAgRP neurons. They are regulated in an opposite fashion and decrease hunger. However, unlike ARCAgRP neurons, ARCPOMC 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 ARCPOMC neurons, rapidly cause satiety when chemo- or optogenetically manipulated. These glutamatergic ARC projections synaptically converge with GABAergic ARCAgRP projections on melanocortin-4 receptor (MC4R)-expressing satiety neurons in the paraventricular hypothalamus (PVH MC4R neurons). Transmission across the ARC Glutamatergic →PVH MC4R synapse is potentiated by the ARCPOMC 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.

AB - Arcuate nucleus (ARC) neurons sense the fed or fasted state and regulate hunger. Agouti-related protein (AgRP) neurons in the ARC (ARCAgRP neurons) are stimulated by fasting and, once activated, they rapidly (within minutes) drive hunger. Pro-opiomelanocortin (ARCPOMC) neurons are viewed as the counterpoint to ARCAgRP neurons. They are regulated in an opposite fashion and decrease hunger. However, unlike ARCAgRP neurons, ARCPOMC 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 ARCPOMC neurons, rapidly cause satiety when chemo- or optogenetically manipulated. These glutamatergic ARC projections synaptically converge with GABAergic ARCAgRP projections on melanocortin-4 receptor (MC4R)-expressing satiety neurons in the paraventricular hypothalamus (PVH MC4R neurons). Transmission across the ARC Glutamatergic →PVH MC4R synapse is potentiated by the ARCPOMC 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.

UR - http://www.scopus.com/inward/record.url?scp=84996922044&partnerID=8YFLogxK

U2 - 10.1038/nn.4442

DO - 10.1038/nn.4442

M3 - مقالة

C2 - 27869800

SN - 1097-6256

VL - 20

SP - 42

EP - 51

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 1

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this