Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes

被引：332

作者：

Romanov, Roman A. ^{[1
]}

Zeisel, Amit ^{[2
]}

Bakker, Joanne ^{[3
]}

Girach, Fatima ^{[1
]}

Hellysaz, Arash ^{[3
]}

Tomer, Raju ^{[4
,5
]}

Alpar, Alan ^{[6
,7
]}

Mulder, Jan ^{[8
]}

Clotman, Frederic ^{[9
]}

Keimpema, Erik ^{[1
]}

Hsueh, Brian ^{[4
,5
]}

Crow, Ailey K. ^{[4
,5
]}

Martens, Henrik ^{[10
]}

Schwindling, Christian ^{[11
]}

Calvigioni, Daniela ^{[1
,3
]}

Bains, Jaideep S. ^{[12
]}

Mate, Zoltan ^{[13
]}

Szabo, Gabor ^{[13
]}

Yanagawa, Yuchio ^{[14
]}

Zhang, Ming-Dong ^{[3
]}

Rendeiro, Andre ^{[15
]}

Farlik, Matthias ^{[15
]}

Uhlen, Mathias ^{[16
]}

Wulff, Peer ^{[17
]}

Bock, Christoph ^{[15
]}

Broberger, Christian ^{[3
]}

Deisseroth, Karl ^{[4
,5
]}

Hokfelt, Tomas ^{[3
]}

Linnarsson, Sten ^{[2
]}

Horvath, Tamas L. ^{[18
]}

Harkany, Tibor ^{[1
,3
]}

机构：

[1] Med Univ Vienna, Dept Mol Neurosci, Ctr Brain Res, Vienna, Austria

[2] Karolinska Inst, Div Mol Neurobiol, Dept Med Biochem & Biophys, Stockholm, Sweden

[3] Karolinska Inst, Dept Neurosci, Stockholm, Sweden

[4] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA

[5] Stanford Univ, CNC Program, Stanford, CA 94305 USA

[6] Hungarian Acad Sci, MTA SE NAP Res Grp Expt Neuroanat & Dev Biol, Budapest, Hungary

[7] Semmelweis Univ, Dept Anat, Budapest, Hungary

[8] Karolinska Inst, Dept Neurosci, Sci Life Labs, Stockholm, Sweden

[9] Catholic Univ Louvain, Inst Neurosci, Lab Neural Differentiat, Brussels, Belgium

[10] Synapt Syst GmbH, Gottingen, Germany

[11] Carl Zeiss Microscopy GmbH, Microscopy Labs Munich, Global Sales Support Life Sci, Munich, Germany

[12] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada

[13] Hungarian Acad Sci, Inst Expt Med, Budapest, Hungary

[14] Gunma Univ, Grad Sch Med, Dept Genet & Behav Neurosci, Maebashi, Gunma, Japan

[15] Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria

[16] Albanova Univ Ctr, Royal Inst Technol, Sci Life Lab, Stockholm, Sweden

[17] Univ Kiel, Inst Physiol, Kiel, Germany

[18] Yale Univ, Comparat Med Sect, Program Integrat Cell Signaling & Neurobiol Metab, Sch Med, New Haven, CT 06520 USA

来源：

NATURE NEUROSCIENCE | 2017年 / 20卷 / 02期

基金：

欧洲研究理事会; 瑞典研究理事会;

关键词：

INNERVATE NEUROENDOCRINE CELLS; SUPRACHIASMATIC NUCLEUS; PARAVENTRICULAR NUCLEUS; MESSENGER-RNA; NEUROMEDIN-S; IDENTIFICATION; EXPRESSION; COMPLEX; PITUITARY; CIRCUIT;

D O I：

10.1038/nn.4462

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The hypothalamus contains the highest diversity of neurons in the brain. Many of these neurons can co-release neurotransmitters and neuropeptides in a use-dependent manner. Investigators have hitherto relied on candidate protein-based tools to correlate behavioral, endocrine and gender traits with hypothalamic neuron identity. Here we map neuronal identities in the hypothalamus by single-cell RNA sequencing. We distinguished 62 neuronal subtypes producing glutamatergic, dopaminergic or GABAergic markers for synaptic neurotransmission and harboring the ability to engage in task-dependent neurotransmitter switching. We identified dopamine neurons that uniquely coexpress the Onecut3 and Nmur2 genes, and placed these in the periventricular nucleus with many synaptic afferents arising from neuromedin S+ neurons of the suprachiasmatic nucleus. These neuroendocrine dopamine cells may contribute to the dopaminergic inhibition of prolactin secretion diurnally, as their neuromedin S+ inputs originate from neurons expressing Per2 and Per3 and their tyrosine hydroxylase phosphorylation is regulated in a circadian fashion. Overall, our catalog of neuronal subclasses provides new understanding of. hypothalamic organization and function.

引用

页码：176 / 188

页数：13

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