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Ren, Jing; Isakova, Alina; Friedmann, Drew; Zeng, Jiawei; Grutzner, Sophie M; Pun, Albert; Zhao, Grace Q; Kolluru, Sai Saroja; Wang, Ruiyu; Lin, Rui; Li, Pengcheng; Li, Anan; Raymond, Jennifer L; Luo, Qingming; Luo, Minmin; Quake, Stephen R; Luo, Liqun
eLife, 10/2019, Letnik: 8Journal Article
Serotonin neurons of the dorsal and median raphe nuclei (DR, MR) collectively innervate the entire forebrain and midbrain, modulating diverse physiology and behavior. To gain a fundamental understanding of their molecular heterogeneity, we used plate-based single-cell RNA-sequencing to generate a comprehensive dataset comprising eleven transcriptomically distinct serotonin neuron clusters. Systematic in situ hybridization mapped specific clusters to the principal DR, caudal DR, or MR. These transcriptomic clusters differentially express a rich repertoire of neuropeptides, receptors, ion channels, and transcription factors. We generated novel intersectional viral-genetic tools to access specific subpopulations. Whole-brain axonal projection mapping revealed that DR serotonin neurons co-expressing vesicular glutamate transporter-3 preferentially innervate the cortex, whereas those co-expressing thyrotropin-releasing hormone innervate subcortical regions in particular the hypothalamus. Reconstruction of 50 individual DR serotonin neurons revealed diverse and segregated axonal projection patterns at the single-cell level. Together, these results provide a molecular foundation of the heterogenous serotonin neuronal phenotypes.
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