학술논문
Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes
Document Type
Academic Journal
Author
Romanov, Roman A.; Zeisel, Amit; Bakker, Joanne; Girach, Fatima; Hellysaz, Arash; Tomer, Raju; Alpar, Alan; Mulder, Jan; Clotman, Frederic; Keimpema, Erik; Hsueh, Brian; Crow, Ailey K.; Martens, Henrik; Schwindling, Christian; Calvigioni, Daniela; Bains, Jaideep S.; Mate, Zoltan; Szabo, Gabor; Yanagawa, Yuchio; Zhang, Ming-Dong; Rendeiro, Andre; Farlik, Matthias; Uhlen, Mathias; Wulff, Peer; Bock, Christoph; Broberger, Christian; Deisseroth, Karl; Hokfelt, Tomas; Linnarsson, Sten; Horvath, Tamas L.; Harkany, Tibor
Source
Nature Neuroscience. February 1, 2017, p176, 13 p.
Subject
Language
English
ISSN
1097-6256
Abstract
Author(s): Roman A Romanov [1]; Amit Zeisel [2]; Joanne Bakker [3]; Fatima Girach [1]; Arash Hellysaz [3]; Raju Tomer [4]; Alán Alpár [5, 6]; Jan Mulder [7]; Frédéric Clotman [8]; [...]
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[sup.+] neurons of the suprachiasmatic nucleus. These neuroendocrine dopamine cells may contribute to the dopaminergic inhibition of prolactin secretion diurnally, as their neuromedin S[sup.+] 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.
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[sup.+] neurons of the suprachiasmatic nucleus. These neuroendocrine dopamine cells may contribute to the dopaminergic inhibition of prolactin secretion diurnally, as their neuromedin S[sup.+] 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.