Molecular and anatomical organization of the dorsal raphe nucleus
- Howard Hughes Medical Institute, Harvard Medical School, United States
- Harvard Medical School, United States
Abstract
The dorsal raphe nucleus (DRN) is an important source of neuromodulators and has been implicated in a wide variety of behavioral and neurological disorders. The DRN is subdivided into distinct anatomical subregions comprised of multiple cell types, and its complex cellular organization has impeded efforts to investigate the distinct circuit and behavioral functions of its subdomains. Here we used single-cell RNA sequencing, in situ hybridization, anatomical tracing, and spatial correlation analysis to map the transcriptional and spatial profiles of cells from the mouse DRN. Our analysis of 39,411 single-cell transcriptomes revealed at least 18 distinct neuron subtypes and 5 serotonergic neuron subtypes with distinct molecular and anatomical properties, including a serotonergic neuron subtype that preferentially innervates the basal ganglia. Our study lays out the molecular organization of distinct serotonergic and non-serotonergic subsystems, and will facilitate the design of strategies for further dissection the DRN and its diverse functions.
Data availability
The sequencing datasets generated in this study are available on the NCBI Gene Expression Omnibus (accession number: GSE134163). R data files containing the processed and annotated scRNA-seq data in the form of Seurat objects are also available on the Harvard Dataverse (https://dataverse.harvard.edu/dataset.xhtml?persistentId=doi:10.7910/DVN/QB5CC8).
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Molecular and anatomical organization of the dorsal raphe nucleusNCBI Gene Expression Omnibus, GSE134163.
Article and author information
Author details
Bernardo L Sabatini
Funding
National Institute of Neurological Disorders and Stroke (NS103226)
- Bernardo L Sabatini
Howard Hughes Medical Institute
- Bernardo L Sabatini
National Institute of Mental Health (MH100568)
- Bernardo L Sabatini
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures were performed in accordance with protocols approved by the Harvard Standing Committee on Animal Care following guidelines described in the U.S. National Institutes of Health Guide for the Care and Use of Laboratory Animals (HMS IACUC protocol #IS00000571). All surgery was performed under isoflurane anesthesia.
Copyright
© 2019, Huang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Molecular and anatomical organization of the dorsal raphe nucleus
eLife 8:e46464.
https://doi.org/10.7554/eLife.46464
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