Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes.

Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes.
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DOI:
10.1038/nn.4462
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发表时间:
2017-03
影响因子:
25
通讯作者:
Harkany T
Harkany T
中科院分区:
医学1区
文献类型:
--
作者:
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

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The hypothalamus contains the highest diversity of neurons in the brain, which use-dependently co-release neurotransmitters and neuropeptides. Investigators have hitherto relied on candidate protein-based tools to correlate behavioral, endocrine and gender traits with hypothalamic neuron identity. Here, we mapped neuronal identities in the hypothalamus by single-cell RNA-sequencing. We distinguish 62 neuronal subtypes producing glutamatergic, dopaminergic or GABAergic codes for synaptic neurotransmission and harboring the ability of task-dependent neurotransmitter switching. We identify dopamine neurons that uniquely co-express Onecut3 and Nmur2 genes, and place 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 because their neuromedin S+ inputs originate from pacemaker 2/3 (Per2/3)-expressing neurons and their tyrosine hydroxylase phosphorylation is circadian regulated. Overall, our catalogue of neuronal subclasses presents new understanding of hypothalamic organization and function.
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