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Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei.

Authors :
Ren J
Isakova A
Friedmann D
Zeng J
Grutzner SM
Pun A
Zhao GQ
Kolluru SS
Wang R
Lin R
Li P
Li A
Raymond JL
Luo Q
Luo M
Quake SR
Luo L
Source :
ELife [Elife] 2019 Oct 24; Vol. 8. Date of Electronic Publication: 2019 Oct 24.
Publication Year :
2019

Abstract

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.<br />Competing Interests: JR, AI, DF, JZ, SG, AP, GZ, SK, RW, RL, PL, AL, QL, ML, SQ, LL No competing interests declared, JR Reviewing editor, eLife<br /> (© 2019, Ren et al.)

Details

Language :
English
ISSN :
2050-084X
Volume :
8
Database :
MEDLINE
Journal :
ELife
Publication Type :
Academic Journal
Accession number :
31647409
Full Text :
https://doi.org/10.7554/eLife.49424