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Nat Neurosci. 2017 Feb;20(2):176-188. doi: 10.1038/nn.4462. Epub 2016 Dec 19.

Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes.

Author information

1
Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna, Austria.
2
Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
3
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
4
Department of Bioengineering &CNC Program, Stanford University, Stanford, California, USA.
5
MTA-SE NAP Research Group of Experimental Neuroanatomy and Developmental Biology, Hungarian Academy of Sciences, Budapest, Hungary.
6
Department of Anatomy, Semmelweis University, Budapest, Hungary.
7
Science for Life Laboratories, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
8
Laboratory of Neural Differentiation, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium.
9
Synaptic Systems GmbH, Göttingen, Germany.
10
Microscopy Labs Munich, Global Sales Support-Life Sciences, Carl Zeiss Microscopy GmbH, Munich, Germany.
11
The Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
12
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
13
Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Japan.
14
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
15
Science for Life Laboratory, Albanova University Center, Royal Institute of Technology, Stockholm, Sweden.
16
Institute of Physiology, Christian Albrechts University, Kiel, Germany.
17
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.

Abstract

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.

PMID:
27991900
DOI:
10.1038/nn.4462
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