Specific connectivity and unique molecular identity of MET receptor tyrosine kinase expressing serotonergic neurons in the caudal dorsal raphe nuclei
Open accessAbstract
Molecular characterization of neurons across brain regions has revealed new taxonomies for understanding functional diversity even among classically defined neuronal populations. Neuronal diversity has become evident within the brain serotonin (5-HT) system, which is far more complex than previously appreciated. However, until now it has been difficult to define subpopulations of 5-HT neurons based on molecular phenotypes. We demonstrate that the MET receptor tyrosine kinase (MET) is specifically expressed in a subset of 5-HT neurons within the caudal part of the dorsal raphe nuclei (DRC) that is encompassed by the classic B6 serotonin cell group. Mapping from embryonic day 16 through adulthood reveals that MET is expressed almost exclusively in the DRC as a condensed, paired nucleus, with an additional sparse set of MET+ neurons scattered within the median raphe. Retrograde tracing experiments reveal that MET-expressing 5-HT neurons provide substantial serotonergic input to the ventricular/subventricular region that contains forebrain stem cells, but do not innervate the dorsal hippocampus or entorhinal cortex. Conditional anterograde tracing experiments show that 5-HT neurons in the DRC/B6 target additional forebrain structures such as the medial and lateral septum and the ventral hippocampus. Molecular neuroanatomical analysis identifies 14 genes that are enriched in DRC neurons, including 4 neurotransmitter/neuropeptide receptors and 2 potassium channels. These analyses will lead to future studies determining the specific roles that 5-HT MET+ neurons contribute to the broader set of functions regulated by the serotonergic system.
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Kast et al. (2017) found that the cDR expressed distinct gene markers compared to pDR, and tracing from these neurons showed cDR was different from the MR and DR in efferent innervation.
“By searching Allen Brain Institute development brain database and using multiplex fluorescent in situ hybridization (ML-FISH), Kast et al. (2017) found that the cDR expressed distinct gene markers comparing to pDR, and tracing from these neurons showed cDR was different from the MR and DR in efferent innervation.”
From Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei (2019) · cites this paper as Kast et al., 2017
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Embracing diversity in the 5-HT neuronal system
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- Authors
- Kast, R. J., Wu, H.-H., Williams, P., Gaspar, P., & Levitt, P.
- Affiliations
- University of Southern California (US)
- Inserm, UMRS-839, Université Pierre et Marie Curie, and Institut du Fer à Moulin, 75005, Paris, France
- Corresponding author
- Levitt, Pat
- Venue
- ACS Chemical Neuroscience
- Publisher
- American Chemical Society (ACS)
- Published
- 2017-05-01
- Volume
- 8
- Issue
- 5
- Pages
- 1053-1064
- ISSN
- 1948-7193 (ISSN-L)
- PMC
- PMC5933970
- OpenAlex
- W2605001211
- Cited by
- 20
- References
- 55
- Citations by year
- 2022: 2 · 2021: 5 · 2020: 5 · 2019: 3 · 2018: 2 · 2017: 3
- FWCI
- 1.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- ACS Chemical Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-11-0004-02)
- National Institute of Mental Health (5 P50 MH096972, R01 MH067842)
- Simms/Mann Family Foundation
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- MET receptor tyrosine kinase, serotonergic neurons, dorsal raphe nucleus, serotonergic system, neuronal subpopulations, molecular phenotypes, serotonergic projections, forebrain, medial septum, lateral septum, ventral hippocampus, retrograde tracing, anterograde tracing, gene expression profiling, potassium channels, neuropeptide receptors
- MeSH terms
- Animals, Immunohistochemistry, Serotonin, Proto-Oncogene Proteins c-met, Mice, Serotonergic Neurons, Dorsal Raphe Nucleus
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