Romanov Roman A, Zeisel Amit, Bakker Joanne, Girach Fatima, Hellysaz Arash, Tomer Raju, Alpár Alán, Mulder Jan, Clotman Frédéric, Keimpema Erik, Hsueh Brian, Crow Ailey K, Martens Henrik, Schwindling Christian, Calvigioni Daniela, Bains Jaideep S, Máté Zoltán, Szabó Gábor, Yanagawa Yuchio, Zhang Ming-Dong, Rendeiro Andre, Farlik Matthias, Uhlén Mathias, Wulff Peer, Bock Christoph, Broberger Christian, Deisseroth Karl, Hökfelt Tomas, Linnarsson Sten, Horvath Tamas L, Harkany Tibor
Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna, Austria.
Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Nat Neurosci. 2017 Feb;20(2):176-188. doi: 10.1038/nn.4462. Epub 2016 Dec 19.
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.
下丘脑包含大脑中种类最为多样的神经元。其中许多神经元能够以使用依赖的方式共同释放神经递质和神经肽。迄今为止，研究人员一直依赖基于候选蛋白的工具，来将行为、内分泌和性别特征与下丘脑神经元身份关联起来。在此，我们通过单细胞RNA测序绘制了下丘脑的神经元身份图谱。我们区分出62种神经元亚型，它们产生用于突触神经传递的谷氨酸能、多巴胺能或γ-氨基丁酸能标记物，并具备进行任务依赖型神经递质转换的能力。我们鉴定出独特地共同表达Onecut3和Nmur2基因的多巴胺神经元，并将它们置于室周核中，许多突触传入纤维来自视交叉上核的神经介素S神经元。这些神经内分泌多巴胺细胞可能在白天对催乳素分泌产生多巴胺能抑制作用，因为它们的神经介素S输入源自表达Per2和Per3的神经元，并且它们的酪氨酸羟化酶磷酸化以昼夜节律方式受到调节。总体而言，我们的神经元亚类目录为下丘脑的组织和功能提供了新的认识。
