title: Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes.
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.
authors.affiliation: Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Roman A
authors.initials: RA
authors.lastname: Romanov
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Amit
authors.initials: A
authors.lastname: Zeisel
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Joanne
authors.initials: J
authors.lastname: Bakker
authors.affiliation: Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Fatima
authors.initials: F
authors.lastname: Girach
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Arash
authors.initials: A
authors.lastname: Hellysaz
authors.affiliation: Department of Bioengineering &CNC Program, Stanford University, Stanford, California, USA.
authors.forename: Raju
authors.initials: R
authors.lastname: Tomer
authors.affiliation: MTA-SE NAP Research Group of Experimental Neuroanatomy and Developmental Biology, Hungarian Academy of Sciences, Budapest, Hungary.|Department of Anatomy, Semmelweis University, Budapest, Hungary.
authors.forename: Alán
authors.initials: A
authors.lastname: Alpár
authors.affiliation: Science for Life Laboratories, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Mulder
authors.affiliation: Laboratory of Neural Differentiation, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Clotman
authors.affiliation: Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Erik
authors.initials: E
authors.lastname: Keimpema
authors.affiliation: Department of Bioengineering &CNC Program, Stanford University, Stanford, California, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Hsueh
authors.affiliation: Department of Bioengineering &CNC Program, Stanford University, Stanford, California, USA.
authors.forename: Ailey K
authors.initials: AK
authors.lastname: Crow
authors.affiliation: Synaptic Systems GmbH, Göttingen, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Martens
authors.affiliation: Microscopy Labs Munich, Global Sales Support-Life Sciences, Carl Zeiss Microscopy GmbH, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schwindling
authors.affiliation: Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna, Austria.|Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Daniela
authors.initials: D
authors.lastname: Calvigioni
authors.affiliation: The Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jaideep S
authors.initials: JS
authors.lastname: Bains
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Máté
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Szabó
authors.affiliation: Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Yuchio
authors.initials: Y
authors.lastname: Yanagawa
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ming-Dong
authors.initials: MD
authors.lastname: Zhang
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Andre
authors.identifier: 0000-0001-9362-5373
authors.initials: A
authors.lastname: Rendeiro
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Farlik
authors.affiliation: Science for Life Laboratory, Albanova University Center, Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.affiliation: Institute of Physiology, Christian Albrechts University, Kiel, Germany.
authors.forename: Peer
authors.initials: P
authors.lastname: Wulff
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Christoph
authors.identifier: 0000-0001-6091-3088
authors.initials: C
authors.lastname: Bock
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Broberger
authors.affiliation: Department of Bioengineering &CNC Program, Stanford University, Stanford, California, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Hökfelt
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sten
authors.initials: S
authors.lastname: Linnarsson
authors.affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Tamas L
authors.initials: TL
authors.lastname: Horvath
authors.affiliation: Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna, Austria.|Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tibor
authors.initials: T
authors.lastname: Harkany
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009479:Neuropeptides / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000502:physiology; D013493:Suprachiasmatic Nucleus / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D009479:Neuropeptides; D018377:Neurotransmitter Agents; C497950:neuromedin S; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine