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Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes.

Authors :
Romanov RA
Zeisel A
Bakker J
Girach F
Hellysaz A
Tomer R
Alpár A
Mulder J
Clotman F
Keimpema E
Hsueh B
Crow AK
Martens H
Schwindling C
Calvigioni D
Bains JS
Máté Z
Szabó G
Yanagawa Y
Zhang MD
Rendeiro A
Farlik M
Uhlén M
Wulff P
Bock C
Broberger C
Deisseroth K
Hökfelt T
Linnarsson S
Horvath TL
Harkany T
Source :
Nature neuroscience [Nat Neurosci] 2017 Feb; Vol. 20 (2), pp. 176-188. Date of Electronic Publication: 2016 Dec 19.
Publication Year :
2017

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 <superscript>+</superscript> neurons of the suprachiasmatic nucleus. These neuroendocrine dopamine cells may contribute to the dopaminergic inhibition of prolactin secretion diurnally, as their neuromedin S <superscript>+</superscript> 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.

Details

Language :
English
ISSN :
1546-1726
Volume :
20
Issue :
2
Database :
MEDLINE
Journal :
Nature neuroscience
Publication Type :
Academic Journal
Accession number :
27991900
Full Text :
https://doi.org/10.1038/nn.4462