Journal
ELIFE
Volume 8, Issue -, Pages -Publisher
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.49424
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Funding
- National Institutes of Health [R01 NS104698, NS057488]
- National Science Foundation
- Ministry of Science and Technology of the People's Republic of China [2015BAI08B02]
- National Natural Science Foundation of China [91432114, 91632302]
- Municipal Government
- NSFC [61721092, 81827901]
- Swiss National Science Foundation
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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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