Functionally distinct POMC-expressing neuron subpopulations in hypothalamus revealed by intersectional targeting

被引：86

作者：

Biglari, Nasim ^{[1
,2
,3
,4
]}

Gaziano, Isabella ^{[1
,2
,3
,4
]}

Schumacher, Jonas ^{[1
,2
,3
,4
]}

Radermacher, Jan ^{[3
,4
,5
]}

Paeger, Lars ^{[3
,4
,5
]}

Klemm, Paul ^{[1
,2
,3
,4
]}

Chen, Weiyi ^{[1
,2
,3
,4
]}

Corneliussen, Svenja ^{[3
,4
,5
]}

Wunderlich, Claudia M. ^{[1
,2
,3
,4
]}

Sue, Michael ^{[1
]}

Vollmar, Stefan ^{[1
]}

Kloeckener, Tim ^{[1
,2
,3
,4
]}

Sotelo-Hitschfeld, Tamara ^{[1
,2
,3
,4
]}

Abbasloo, Amin ^{[1
]}

Edenhofer, Frank ^{[6
]}

Reimann, Frank ^{[7
,8
]}

Gribble, Fiona M. ^{[7
,8
]}

Fenselau, Henning ^{[2
,3
,4
,9
]}

Kloppenburg, Peter ^{[3
,4
,5
]}

Wunderlich, Frank T. ^{[1
,2
,3
,4
]}

Bruening, Jens C. ^{[1
,2
,3
,4
,10
]}

机构：

[1] Max Planck Inst Metab Res, Dept Neuronal Control Metab, Cologne, Germany

[2] Univ Hosp Cologne, Policlin Endocrinol Diabet & Prevent Med PEDP, Cologne, Germany

[3] Univ Cologne, Excellence Cluster Cellular Stress Responses Agin, Cologne, Germany

[4] Univ Cologne, Ctr Mol Med Cologne CMMC, Cologne, Germany

[5] Univ Cologne, Bioctr, Inst Zool, Cologne, Germany

[6] Leopold Franzens Univ Innsbruck, Inst Mol Biol, Innsbruck, Austria

[7] Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge, England

[8] Addenbrookes Hosp, MRC, Metab Dis Unit, Cambridge, England

[9] Max Planck Inst Metab Res, Res Grp Synapt Transmiss Energy Homeostasis, Cologne, Germany

[10] Natl Ctr Diabet Res DZD, Ingolstadter Landstr 1, Neuherberg, Germany

来源：

NATURE NEUROSCIENCE | 2021年 / 24卷 / 07期

基金：

欧洲研究理事会;

关键词：

D O I：

10.1038/s41593-021-00854-0

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Pro-opiomelanocortin (POMC)-expressing neurons in the arcuate nucleus of the hypothalamus represent key regulators of metabolic homeostasis. Electrophysiological and single-cell sequencing experiments have revealed a remarkable degree of heterogeneity of these neurons. However, the exact molecular basis and functional consequences of this heterogeneity have not yet been addressed. Here, we have developed new mouse models in which intersectional Cre/Dre-dependent recombination allowed for successful labeling, translational profiling and functional characterization of distinct POMC neurons expressing the leptin receptor (Lepr) and glucagon like peptide 1 receptor (Glp1r). Our experiments reveal that POMCLepr+ and POMCGlp1r+ neurons represent largely nonoverlapping subpopulations with distinct basic electrophysiological properties. They exhibit a specific anatomical distribution within the arcuate nucleus and differentially express receptors for energy-state communicating hormones and neurotransmitters. Finally, we identify a differential ability of these subpopulations to suppress feeding. Collectively, we reveal a notably distinct functional microarchitecture of critical metabolism-regulatory neurons. Biglari et al. reveal subgroups of arcuate nucleus hypothalamic neurons that exhibit distinct molecular signatures and feeding-regulatory functions, thus uncovering new regulatory principles in body weight control.

引用

页码：913 / 929

页数：17

共 64 条

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