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

被引：223

作者：

Fenselau, Henning ^{[1
]}

Campbell, John N. ^{[1
]}

Verstegen, Anne M. J. ^{[1
]}

Madara, Joseph C. ^{[1
]}

Xu, Jie ^{[1
]}

Shah, Bhavik P. ^{[1
]}

Resch, Jon M. ^{[1
]}

Yang, Zongfang ^{[1
]}

Mandelblat-Cerf, Yael ^{[1
]}

Livneh, Yoav ^{[1
]}

Lowell, Bradford B. ^{[1
,2
]}

机构：

[1] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA

[2] Harvard Med Sch, Program Neurosci, Boston, MA 02115 USA

来源：

NATURE NEUROSCIENCE | 2017年 / 20卷 / 01期

关键词：

HYPOTHALAMIC PROOPIOMELANOCORTIN NEURONS; POMC NEURONS; FOOD-INTAKE; PARAVENTRICULAR NUCLEUS; FRAMESHIFT MUTATION; ENERGY-EXPENDITURE; OBESITY; MELANOCORTIN; OXYTOCIN; AGRP;

D O I：

10.1038/nn.4442

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 (PVHMc4R neurons). Transmission across the ARC(GIutamatergic)-> PvH(MC4R) synapse is potentiated by the ARCPcmc neuron-derived MC4R agonist, ot-melanocyte stimulating hormone (alpha-MSH). This excitatory ARC -> PVH satiety circuit, and its modulation by alpha-MSH, provides insight into regulation of hunger and satiety.

引用

页码：42 / 51

页数：10

共 47 条

[1] AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training [J].