Cited by 304Single-cell and spatial transcriptomicsNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

The DOI matches its Crossref record; 95 of the 97 references it cites were found in a registry or an index; none of the 66 sources its claims cite is checked for support yet.

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

Open access

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·2019·eLife

DOI 10.7554/elife.49424PMC PMC6812963

Published version of a preprint

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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.

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TL;DR

Plate-based single-cell RNA-sequencing of 999 mouse dorsal and median raphe serotonin neurons identified 11 transcriptomic clusters with distinct spatial, molecular, and projection features. Intersectional viral tracing and single-neuron reconstruction showed that Vglut3+ and Trh+ DR serotonin neurons preferentially innervate cortical versus subcortical targets, while individual DR serotonin neurons have highly diverse whole-brain arborization patterns.

Key findings

scRNA-seq of 999 Tph2+ serotonin neurons from 14 adult mouse brains resolved 11 transcriptomic clusters: six principal DR clusters (DR-1–6), one caudal DR cluster (cDR), and four median raphe clusters (MR-1–4); HCR-smFISH with 16 markers mapped these clusters to pDR, cDR, or MR locations.
Co-transmitter and neuropeptide expression was heterogeneous: 65% of serotonin neurons expressed Vglut3, 35% expressed Gad1, Gad2, or both, 13% expressed Vglut3 plus Gad1/Gad2, and 14% expressed none of these glutamate/GABA markers; Trh was expressed in 14% and Crh in 7% of serotonin neurons.
Intersectional Sert-Flp with Vglut3-Cre or Trh-Cre showed that Vglut3+ pDR serotonin neurons preferentially innervate cortical regions, whereas Trh+ pDR serotonin neurons innervate subcortical regions including anterior/medial hypothalamus and thalamic nuclei; whole-brain mapping used n = 3 mice per genotype.
Reconstruction of 50 individual DR serotonin neurons revealed total axon lengths from 1.9 cm to 26.3 cm, with cortex-projecting neurons having the longest axons; 37/50 projections were unilateral, and 34/46 forebrain-projecting neurons had >80% of forebrain axon length in either cortical or subcortical regions.

Methods

Serotonin neurons were labeled using Sert-Cre;Ai14 mice, acutely dissociated from brain slices of postnatal day 40–45 mice (six females, eight males), FACS-sorted, and processed with Smart-seq2; 709 cells came from eight MR/pDR/cDR samples and 290 cells from six pDR-only samples, yielding 999 cells after QC.
Clustering used Seurat v3.0 with PCA and Louvain clustering; HCR-based smFISH against 16 cluster markers plus Tph2 was used to map transcriptomic clusters anatomically.
For projection mapping, Sert-Flp mice were crossed with Vglut3-Cre or Trh-Cre and injected with AAV-CreON/FlpON-mGFP; brains were cleared with AdipoClear, imaged by light-sheet microscopy, segmented with a 3D U-Net, and aligned to the Allen Common Coordinate Framework. Single-neuron reconstructions used dual-AAV sparse labeling and fMOST in 14 Sert-Cre mice.

Limitations

Stated: single-neuron reconstruction was limited in scope to 50 reconstructed cells out of approximately 9000 DR serotonin neurons, and larger-scale reconstruction integrated with molecular identity and function is needed.
Stated: whole-brain tracing showed inter-individual variability in total labeled axons and detailed projection patterns, and heterogeneity within Vglut3+ or Trh+ populations may contribute; larger experiments or single-cluster Cre lines are required.
Stated/evident: the Sert-Flp line can drive reporter expression outside raphe serotonin neurons due to transient developmental Sert expression; the paper also notes that whether Gad1/Gad2+ serotonin neurons actually release GABA remains to be determined, and MR cluster anatomical organization was less obvious with clusters more intermingled.

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Crossref · 10.7554/elife.49424

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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These 999 MR and DR serotonin neurons comprised 11 clusters (Figure 1B; Figure 1—figure supplement 2).”
- Also stated in: § Abstract · plain
  “we used plate-based single-cell RNA-sequencing to generate a comprehensive dataset comprising eleven transcriptomically distinct serotonin neuron clusters.”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Results > Single-cell RNA-sequencing defines 11 transcriptomic clusters of serotonin neurons in the dorsal and median raphe
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Instead, Trh+ serotonin axons project to the anterior and medial hypothalamus, posterior amygdala, and the lateral geniculate nucleus in the thalamus, none of which were targeted by Vglut3+ axons (Figure 6D).”
- Also stated in: § Abstract · plain
  “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.”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Results > Viral-genetic tools to access different serotonin neuron subtypes
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In the paper
“Comparing marker genes enriched in R1–R3-derived serotonin neurons from Okaty et al. and MR-1–MR-4 transcriptomic clusters from our current study (Figure 3—figure supplement 4) indeed suggests an approximate correspondence: R1-derived serotonin neurons correspond to our MR-1 cluster, R2 to MR-4 cluster, and R3 to both MR-2 and MR-3 clusters.”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Discussion > Relationship between molecular identity and cell body distribution
What the sources say
- Not checked yetcites Okaty et al., 2015 source
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In the paper
“Our transcriptome data suggest that each DR/MR serotonin neuron type can be distinguished from others by the expression of two marker genes (Figure 1D; Figure 3—figure supplement 1–3), supporting the view that neuronal subtypes are generally specified by unique combination of genes rather than single genes (Li et al., 2017).”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Discussion > Relationship between molecular identity and projection-defined serotonin sub-systems
What the sources say
- Not checked yetcites Li et al., 2017
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In the paper
“By contrast, we could not discern obvious difference in spatial distributions among the four MR types, despite the fact that MR serotonin neurons have heterogenous developmental origin (Jensen et al., 2008).”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Discussion > Relationship between molecular identity and cell body distribution
What the sources say
- Not checked yetcites Jensen et al., 2008 source
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None of the sources cited for this claim have been checked yet.
In the paper
“The rest of the DR serotonin neurons were divided into thalamus-projecting and brainstem/cerebellum-projecting groups based on the highest density of axons (Figure 8—figure supplement 3B,C), one of which likely projecting to the spinal cord (brain 36) as previously reported (Bowker et al., 1981; Bowker et al., 1982).”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Results > Whole-brain axonal arborization patterns of individual serotonin neurons
What the sources say
- Not checked yetcites Bowker et al., 1981 source
- Not checked yetcites Bowker et al., 1982 source
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It may state two separate claims as one.
In the paper
“Gene expression patterns of specific serotonin neuron clusters can in principle allow genetic access to these specific subpopulations for anatomical tracing, physiological recording, and functional perturbation (Luo et al., 2018).”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Results > Viral-genetic tools to access different serotonin neuron subtypes
What the sources say
- Not checked yetcites Luo et al., 2018 source
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, our HCR-smFISH experiments support the notion that Clusters 1–6 correspond to pDR serotonin neurons, Cluster 7 corresponds to cDR serotonin neurons, and Clusters 8–11 correspond to MR serotonin neurons.”
- Also stated in: § Abstract · plain
  “Systematic in situ hybridization mapped specific clusters to the principal DR, caudal DR, or MR.”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Results > Anatomical organization of transcriptomically defined serotonin clusters
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In the paper
“It has been reported that vesicular monoamine transporters (Slc8a1 for Vmat1; Slc8a2 for Vmat2) can transport GABA into synaptic vesicles (Stensrud et al., 2014), and virtually all serotonin neurons expressed Vmat2 (Figure 1—figure supplement 1D; Figure 4A left).”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Results > Molecular properties of MR and DR serotonin neurons
What the sources say
- Not checked yetcites Stensrud et al., 2014 source
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Probably not a substantial claim.
In the paper
“However, DR and MR contain not only serotonin neurons but also GABAergic and glutamatergic neurons that do not express Tph2 (and hence do not release serotonin), some of which may project to the same target regions (McDevitt et al., 2014).”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Results > Viral-genetic tools to access different serotonin neuron subtypes
What the sources say
- Not checked yetcites McDevitt et al., 2014 source
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In the paper
“Transcription factors (TFs) have been shown to be the best molecular feature for cell type definition (Schaum et al., 2018).”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Results > Molecular properties of MR and DR serotonin neurons
What the sources say
- Not checked yetcites Schaum et al., 2018 source
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“DR serotonin neurons derive entirely from rhombomere 1 of the developing mouse brain, whereas MR serotonin neurons derive predominantly from rhombomeres 1, 2, and 3 (Alonso et al., 2013; Bang et al., 2012; Jensen et al., 2008).”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Introduction
What the sources say
- Not checked yetcites Alonso et al., 2013 source
- Not checked yetcites Bang et al., 2012
- Not checked yetcites Jensen et al., 2008 source
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Evidence has suggested that the DR and MR serotonin systems differ in developmental origin, connectivity, physiology, and behavioral function (Alonso et al., 2013; Calizo et al., 2011; Okaty et al., 2019).”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Introduction
What the sources say
- Not checked yetcites Alonso et al., 2013 source
- Not checked yetcites Calizo et al., 2011 source
- Not checked yetcites Okaty et al., 2019 source
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None of the sources cited for this claim have been checked yet.
In the paper
“The MR serotonin neurons project to structures near the midline, whereas the DR serotonin neurons target more lateral regions (Jacobs and Azmitia, 1992; Muzerelle et al., 2016; Vertes, 1991; Vertes et al., 1999).”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Introduction
What the sources say
- Not checked yetcites Jacobs and Azmitia, 1992
- Not checked yetcites Muzerelle et al., 2016 source
- Not checked yetcites Vertes, 1991 source
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In the paper
“Groups B1–B3 are located in the medulla and provide descending serotonergic innervation to the spinal cord and other parts of the medulla. Groups B4–B9 are located in the pons and midbrain, including the dorsal raphe (DR; groups B6 and B7) and median raphe (MR; groups B5 and B8) nucleus, and provide ascending innervation to the forebrain and midbrain.”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Introduction
What the sources say
- Not checked yetcites Dahlström and Fuxe, 1964
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“As a specific example, we recently found that DR serotonin neurons that project to frontal cortex and amygdala constitute two sub-systems with distinct cell body locations, axonal collateralization patterns, biased inputs, physiological response properties, and behavioral functions (Ren et al., 2018).”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Introduction
What the sources say
- Not checked yetcites Ren et al., 2018 source
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None of the sources cited for this claim have been checked yet.
In the paper
“In neural circuits where cell types have been well studied by anatomical and physiological methods, there is an excellent correspondence between cell types defined by transcriptomes and the classical methods (Li et al., 2017; Shekhar et al., 2016).”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Introduction
What the sources say
- Not checked yetcites Li et al., 2017
- Not checked yetcites Shekhar et al., 2016 source
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Serotonin neurons in the central nervous system are spatially clustered in the brainstem, originally designated as groups B1–B9 (Dahlström and Fuxe, 1964).”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Introduction
What the sources say
- Not checked yetcites Dahlström and Fuxe, 1964
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Collectively,~12,000 serotonin neurons from the DR and MR in mice (~0.015% of all CNS neurons) innervate the entire forebrain (Ishimura et al., 1988) and modulate diverse physiological and behavioral functions.”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Discussion
What the sources say
- Not checked yetcites Ishimura et al., 1988 source
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The MR serotonin neurons derive from three separate rhombomeres (R1–R3), and Okaty et al. sampled these three populations separately, allowing us to ask the question of whether developmental origins correspond to transcriptomic clusters in adult.”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Discussion > Relationship between molecular identity and cell body distribution
What the sources say
- Not checked yetcites Okaty et al., 2015 source
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In the paper
“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.”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Discussion > Relationship between molecular identity and cell body distribution
What the sources say
- Not checked yetcites Kast et al., 2017 source
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It may state two separate claims as one.
In the paper
“The cDR has been suggested to be more similar to the MR than to the pDR in afferent innervation (Commons, 2015).”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Discussion > Relationship between molecular identity and cell body distribution
What the sources say
- Not checked yetcites Commons, 2015 source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In our previous study, we characterized two projection-defined parallel DR serotonin sub-systems.”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Discussion > Relationship between molecular identity and projection-defined serotonin sub-systems
What the sources say
- Not checked yetcites Ren et al., 2018 source
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Probably not a substantial claim.
In the paper
“We found that serotonin neurons that project to the orbitofrontal cortex (OFC) and central amygdala (CeA) differ in input and output patterns, physiological response properties, and behavioral functions (Ren et al., 2018).”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Discussion > Relationship between molecular identity and projection-defined serotonin sub-systems
What the sources say
- Not checked yetcites Ren et al., 2018 source
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It may state two separate claims as one.
In the paper
“These data support and extend our previous finding (Ren et al., 2018) for the preferential ventral pDR location of Vglut3+ serotonin neurons, which is highly expressed in DR-4 and DR-5 clusters.”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Discussion > Relationship between molecular identity and cell body distribution
What the sources say
- Not checked yetcites Ren et al., 2018 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“Because DR serotonin neurons derive exclusively from rhombomere 1 (R1), and the single-cell RNA-seq data was obtained from just 8 cells, the Okaty et al. dataset is limited in providing information about heterogeneity within DR serotonin neurons.”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Discussion > Relationship between molecular identity and cell body distribution
What the sources say
- Not checked yetcites Okaty et al., 2015 source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“Forebrain-projecting serotonin neurons have been estimated to have very long axons based on the total serotonin fiber density and number of serotonin neurons (Wu et al., 2014).”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Results > Whole-brain axonal arborization patterns of individual serotonin neurons
What the sources say
- Not checked yetcites Wu et al., 2014
Strength:hedged· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Given that CeA-projecting DR serotonin neurons do not innervate most of the hypothalamus (Ren et al., 2018), and Trh+ serotonin neurons only partially innervate CeA, these two populations are at most partially overlapping.”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Discussion > Relationship between molecular identity and projection-defined serotonin sub-systems
What the sources say
- Not checked yetcites Ren et al., 2018 source
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“For example, several studies have reported that subgroups of serotonin neurons in the MR and DR express Vglut3 and indeed, subsequent slice recording confirmed that serotonin terminals can co-release glutamate and serotonin (Domonkos et al., 2016; Liu et al., 2014; Ren et al., 2018; Sengupta et al., 2017; Varga et al., 2009; Wang et al., 2019).”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Discussion > Integrating multiple features within individual serotonin sub-systems
What the sources say
- Not checked yetcites Domonkos et al., 2016 source
- Not checked yetcites Liu et al., 2014 source
- Not checked yetcites Ren et al., 2018 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“While the reported projection and arborization complexity of individual DR neurons appear qualitatively similar to our findings, these studies cannot be directly compared because the Gagnon and Parent study did not validate the serotonin identity of individually traced DR neurons, which could include Tph2-negative long-distance projecting GABAergic and glutamatergic neurons (Bang and Commons, 2012”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Discussion > Insights from single-cell reconstruction
What the sources say
- Not checked yetcites Gagnon and Parent, 2014
- Not checked yetcites Bang and Commons, 2012
Load-bearingStrength:hedged· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“Our previous study suggests that DR serotonin sub-systems have biased input but segregated output (Ren et al., 2018).”
§ Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei > Discussion > Integrating multiple features within individual serotonin sub-systems
What the sources say
- Not checked yetcites Ren et al., 2018 source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.

79 of 79

The paper relies on this without support.
The heterogeneity of DR and MR serotonin neurons must be reflected at the molecular level.
“Ultimately, the heterogeneity of DR and MR serotonin neurons must be reflected at the molecular level.”
The paper relies on this without support.
The DR contains approximately 9000 serotonin neurons.
“our study is still limited by the scope (50 reconstructed cells out of 9000 DR serotonin neurons).”

2 of 2

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Vglut3 is assigned two different gene symbols
Minor
The results identify Vglut3 as Slc17a8, but the Animals section calls the Vglut3-Cre line Slc18a8-Cre.

1 of 1

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Macosko, E. Z., Basu, A., Satija, R., Nemesh, J., Shekhar, K., Goldman, M., Tirosh, I., Bialas, A. R., Kamitaki, N., Martersteck, E. M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.002 · Cited by 7,110
A robust and high-throughput Cre reporting and characterization system for the whole mouse brain
Madisen, L., Zwingman, T. A., Sunkin, S. M., Oh, S. W., Zariwala, H. A., Gu, H., Ng, L. L., Palmiter, R. D., Hawrylycz, M. J., Jones, A. R., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2467 · Cited by 6,907 · cited 3×
“The Ai14 tdTomato Cre reporter mice (JAX Strain 7914) Ren et al. eLife 2019;8:e49424.”
BackgroundInfluential
Full-length RNA-seq from single cells using Smart-seq2
Picelli, S., Faridani, O. R., Björklund, Å. K., Winberg, G., Sagasser, S., & Sandberg, R. (2014) · Nature Protocols · doi:10.1038/nprot.2014.006 · Cited by 4,137 · cited 1×
“cDNA synthesis and library preparation were performed using the Smart-seq2 protocol (Picelli et al., 2014).”
Method
Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq
Zeisel, A., Muñoz-Manchado, A. B., Codeluppi, S., Lönnerberg, P., La Manno, G., Juréus, A., Marques, S., Munguba, H., He, L., Betsholtz, C., et al. (2015) · Science · doi:10.1126/science.aaa1934 · Cited by 3,124 · cited 1×
“…powerful tool for unbiased identification of transcriptomic cell types in the brain (Darmanis et al., 2015; Li et al., 2017; Mickelsen et al., 2019; Rosenberg et al., 2018; Saunders et al., 2018; Tasic et al., 2016; Tasic et al., 2018; Welch et al., 2019; Zeisel et al., 2018; Zeisel et al., 2015).”
Method
Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris
The Tabula Muris Consortium, coordination, O., coordination, L., processing, O. C. A., sequencing, L. P. A., analysis, C. D., annotation, C. T., Writing group, Supplemental text writing group, & Principal investigators (2018) · Nature · doi:10.1038/s41586-018-0590-4 · Cited by 2,842 · cited 3×
“Transcription factors Transcription factors (TFs) have been shown to be the best molecular feature for cell type definition (Schaum et al., 2018).”
BackgroundMethodInfluential

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Items 201–300 of 302

The role of dorsal raphe nucleus neuropeptides in reward and aversion
Braden, K., & Castro, D. C. (2025) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2025.1553470 · Cited by 4
“…again proven limited with the majority using chemical or genetic manipulations to select for only serotonergic cells in their downstream analyses of neurotransmitter expression (Okaty et al., 2020; Ren et al., 2019), rather than considering other neuronal cell types that are present in the DRN.”
Activity in serotonergic axons in visuomotor areas of cortex is modulated by the recent history of visuomotor coupling
Yogesh, B., & Keller, G. B. (2025) · Peer Community Journal · doi:10.24072/pcjournal.592 · Cited by 5
The lateral habenula as a master regulator of innate and learned social behaviors
Dodis, G. E., Choi, S., & Flanigan, M. E. (2025) · Psychopharmacology · doi:10.1007/s00213-025-06911-x · Cited by 3
“The LHb both directly excites serotonin neurons in the DR as well as indirectly inhibits them through di-synaptic connections with local DR inhibitory neurons (Pollak Dorocic et al. 2014; Ren et al. 2019; Okaty et al. 2020).”
Shared and divergent alteration of whole-brain connectivity and sensory deficits in multiple autism mouse models
Hsu, T.-T., Chen, C.-P., Lin, M.-H., Hung, T.-E., Huang, T., Wang, C.-Y., & Hsueh, Y. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03340-2 · Cited by 3
Serotonin modulates nucleus accumbens circuits to suppress aggression in mice
Zhang, Z., Touponse, G. C., Alderman, P. J., Yassine, T. A., Pomrenze, M. B., Harris, T., Shank, A. N., Malenka, R. C., & Eshel, N. (2026) · Nature Communications · doi:10.1038/s41467-026-69254-x · Cited by 4
“DR serotonin neurons can co-express gene markers associated with glutamatergic or GABAergic transmission, or both 41,42 .”
Early life chronic stress-disrupted activity of the dorsal raphe nucleus selectively drives behavioral impairments
Varga, Z. K., Golla, A., & Kermen, F. (2026) · Communications Biology · doi:10.1038/s42003-026-09855-w · Cited by 3
Separate or inseparable? Serotonin and dopamine system interactions may underlie the therapeutic potential of psilocybin for anorexia nervosa
McCoy, K., Reed, F. M., Conn, K., & Foldi, C. J. (2025) · Physiology & Behavior · doi:10.1016/j.physbeh.2025.114957 · Cited by 3
“DRN 5-HT neurons have been shown to innervate regions integral to both reward processing and executive function such as the PFC, NAc and VTA [110] and also receive direct input from various brain regions including; GABAergic innervation from the VTA [71] and NAc [103] and glutamatergic innervation…”
Ultrabright chemical labeling enables rapid neural connectivity profiling in large tissue samples
Zhong, S., Zhang, X., Gao, X., Li, Z., Huang, L., Guo, Q., Gong, R., Ren, J., Luo, M., & Lin, R. (2025) · Neuron · doi:10.1016/j.neuron.2025.08.022 · Cited by 5
Self-citation
In vivo brain levels of acetylcholine and 5‐hydroxytryptamine after oleoylethanolamide or palmitoylethanolamide administrations are mediated by PPARα engagement
Murillo‐Rodríguez, E., Arankowsky‐Sandoval, G., Budde, H., Imperatori, C., Machado, S. E. D. C., Yamamoto, T., Yadollahpour, A., & Torterolo, P. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.15409 · Cited by 3
“There are two non-exclusive explanations for these findings: (i) OEA and PEA might activate PPARα on cholinergic neurons placed in the basal forebrain and the mesopontine serotoninergic neurons that project towards the basal forebrain (Morin & Meyer-Bernstein, 1999; Ren et al., 2019).”
Developmental Disruption of Erbb4 in Pet1+ Neurons Impairs Serotonergic Sub-System Connectivity and Memory Formation
Barettino, C., Ballesteros-Gonzalez, Á., Aylón, A., Soler-Sanchis, X., Ortí, L., Díaz, S., Reillo, I., García-García, F., Iborra, F. J., Lai, C., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.770458 · Cited by 3
“Next, we aimed to better characterize the molecular identity of adult ErbB4+ serotonergic neurons taking advantage of transcriptomic data from recent single cell RNAseq of adult Sert and/or Pet1-expressing serotonergic neurons (Okaty et al., 2020; Ren et al., 2019).”
BackgroundMethodInfluential
Activation of ventral pallidum-projecting neurons in the nucleus accumbens via 5-HT2C receptor stimulation regulates motivation for wheel running in male mice
Niitani, K., Nishida, R., Futami, Y., Nishitani, N., Deyama, S., & Kaneda, K. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110181 · Cited by 3
Serotonergic inhibition of responding for conditioned but not primary reinforcers
McDevitt, R. A., Marino, R. A. M., Tejeda, H. A., & Bonci, A. (2021) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2021.173186 · Cited by 3
Concerted modulation of spontaneous behavior and time-integrated whole-brain neuronal activity by serotonin receptorsPreprint
Friedmann, D., Gonzalez, X., Moses, A. M., Watts, T., Degleris, A., Ticea, N., Song, J. H., Datta, S. R., Linderman, S. W., & Luo, L. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.08.02.606282 · Cited by 4
“…illustrate the effect of serotonin modulation on highly specific brain regions, consistent with the highly specific collateralization patterns of subpopulations of serotonin neurons 42,44 , and suggest that differential serotonin modulation can be used as a means to subdivide brain regions.”
Self-citation
Novel insights into the mechanisms of growth cone dynamics during axon pathfinding
Pérez-Ferrer, I., & Herrera, E. (2025) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2025.103073 · Cited by 2
From rodents to humans: Conserved codistribution of dopaminergic with serotonergic neurons in the dorsal raphe nucleus and their molecular characterization
García-Verdugo, M., Rodríguez-Martín, P., Gustincich, S., Lanciego, J. L., Murer, M. G., Jercog, P. E., & Moratalla, R. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.107173 · Cited by 2
Primary and nonprimary auditory cortex connectivity with brain regions involved in cognitive and emotional processing: in mouse and human
Köse, B., Özkan, M., Güneş, Y. C., Algın, O., & Çavdar, S. (2026) · Hearing Research · doi:10.1016/j.heares.2026.109538 · Cited by 2
Neurodevelopmental effects of early life stress: PFC and cognition
Rachmany, L., Abreu, F. F., Walker, V., O'Neill, O. S., Sargin, D., & Teixeira, C. M. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106663 · Cited by 5
Robust serotonin activation of the kisspeptin GnRH pulse generator in male and female mice
Morris, P. G., Liu, X., Birt, E., Vas, S., Ruiz-Cruz, M., Schafer, D. M., McQuillan, H. J., & Herbison, A. E. (2026) · Endocrinology · doi:10.1210/endocr/bqag034 · Cited by 2
“The precise identity of the raphe subpopulation innervating the ARN KISS neurons is not known but approximately 5% of dorsal raphe serotonin neurons innervate the ARN (31) and these cells are likely to be part of the subtype co-expressing GABA and thyrotropin-releasing hormone (32).”
Deciphering brain cellular and behavioral mechanisms: Insights from single‐cell and spatial RNA sequencing
Chen, R., Nie, P., Wang, J., & Wang, G. (2024) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1865 · Cited by 3
“Different cell types may play roles in various parts of the network (Poirazi et al., 2003; Ren et al., 2019; Tran et al., 2021; Yuste, 2015).”
Modulation of dorsal raphe nucleus connectivity and serotonergic signalling to the insular cortex in the prosocial effects of chronic fluoxetine
Payet, J. M., Baratta, M. V., Christianson, J. P., Lowry, C. A., & Hale, M. W. (2025) · Neuropharmacology · doi:10.1016/j.neuropharm.2025.110406 · Cited by 2
“Serotonergic neurons originating from the DR send projections along the whole extent of the IC, and particularly the granular division (Linley et al., 2013; Ren et al., 2019).”
Reciprocal lateral hypothalamic and raphé GABAergic projections promote wakefulnessPreprint
Gazea, M., Furdan, S., Sere, P., Oesch, L., Molnár, B., Giovanni, G. D., Fenno, L. E., Ramakrishnan, C., Mattis, J., Deisseroth, K. A., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.11.04.367722 · Cited by 3
Anticipatory attractors, functional neurochemistry and “Throw & Catch” mechanisms as illustrations of constructivism
Trofimova, I. N. (2022) · Reviews in the Neurosciences · doi:10.1515/revneuro-2022-0120 · Cited by 1
“…be done, but several remarkable studies have shown already that NT receptors are not evenly distributed in the brain (Delay-Goyet et al. 1987; Goulas et al. 2021; Hamel and Beaudet 1984; Lena et al. 1999; Mansour et al. 1987; Peckys and Landwehrmeyer 1999; Ren et al. 2019; Sharif and Hughes 1989).”
Background
Role of Magnetic Nanomaterials in Biotechnological Applications
Mohapatra, S. D., Senapati, S., Giri, J., Bhattacharya, A., Dash, M., Bastia, T. K., Rath, P., & Panda, A. K. (2024) · Nanostructure science and technology · doi:10.1007/978-3-031-44599-6_15 · Cited by 1
The organization of serotonergic fibers in the Pacific angelshark brain: neuroanatomical and supercomputing analyses
Janušonis, S., Metzler, R., & Vojta, T. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1602116 · Cited by 1
“Recent single-cell RNA-seq studies have revealed an enormous transcriptional diversity of serotonergic neurons (Okaty et al., 2019; Ren et al., 2019; Okaty et al., 2020).”
Brain Monoamine Deficits in the CD Mouse Model of Williams–Beuren Syndrome
Aman, C., Gréa, H., Rousseau, A., Allain, A., Pietropaolo, S., Deurwaerdère, P. D., & Lemaire, V. (2025) · Biomolecules · doi:10.3390/biom15101382 · Cited by 1
“The anatomical data suggest some kind of specificity of the distribution of 5-HT neurons and their projections [28–30], but the neurons that innervate the hypothalamus are also innervating other brain regions we sampled.”
Context-dependent serotonin signaling links dietary quality to foraging decisions
Feng, L., Marquina-Solis, J., Yue, L., Harnagel, A., Greenfeld, Y., & Bargmann, C. I. (2025) · Nature Communications · doi:10.1038/s41467-025-65491-8 · Cited by 15
“Understanding information ﬂ ow requires detailed identi ﬁ cation of the functional connections between serotonin-and serotonin-receptor expressing neurons in speci ﬁ c behavioral contexts 35 – 37 .”
Causal links between serotonin dynamics and cued fear learning: evidence from experimental studies
Badripour, A., & Kim, T. (2026) · Frontiers in Computational Neuroscience · doi:10.3389/fncom.2026.1750926 · Cited by 1
Dorsal Raphe Revisited: A Systems Neuroscience Lens on Psychedelic Drug Action
Kwan, A. C. (2026) · Psychedelic Medicine · doi:10.1177/28314425261429232 · Cited by 1
“Advances in genomics and transcriptomics have clari ﬁ ed the full complement of 5-HT receptor subtypes 62 and revealed that serotonergic and GABAergic neurons in the mouse dorsal raphe preferentially express 5-HT 1A and 5-HT 2C receptors, respectively 63,64 (Fig.”
Bidirectional interactions between neuromodulatory systems and the cerebellum in brain function
Kim, T., Park, H., Jun, S., Park, J., Yamamoto, Y., & Tanaka, K. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106716 · Cited by 1
Thyrotropin-releasing hormone and dopaminergic systems interact in the ventral tegmental area to regulate food intake in rats
Srivastava, A., Waghade, A. M., Sahoo, D., Divyajyoti, S., Patil, A., Chattopadhyay, A., Kokare, D. M., & Singru, P. S. (2026) · Neuropharmacology · doi:10.1016/j.neuropharm.2026.111091 · Cited by 1
Sex-sensitive serotonergic signaling in psychedelic pharmacology
Nasini, S., Barzon, B., Casile, A., Richardson, B., Gobbi, G., & Comai, S. (2026) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2026.07.006 · Cited by 1
Architecture of the serotonergic projectome in the mouse brain
Song, J. H., Friedmann, D., Wu, Y., Moses, A., Baruni, J., Yuan, Y., Rana, I., Zhao, K., Sten, T. H., Wang, Q., et al. (2026) · Cell · doi:10.1016/j.cell.2026.08.022 · Cited by 1
Self-citation
Diff-ATAC-STARR-Seq: A Method for Genome-Wide Functional Screening of Enhancer Activity in Vivo
Nagayasu, K., Andoh, C., Shirakawa, H., & Kaneko, S. (2022) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b22-00400 · Cited by 1
A pipeline for identification and validation of brain targets for weight loss
Tsang, A. H. K., & Blouet, C. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00803-w · Cited by 1
“Excitingly, several reports indicate strong molecular, neuroanatomical and functional segregation of DRN neurons [3, 5], opening the possibility of refined targeting of DRN populations with minimal off-target effects.”
Neurocognitive Dysfunction and predictors in non-CNS cancer patients: Rationale and methods for the neuro-oncology research at a South African academic hospital
Lentoor, A. G., & Motsamai, T. B. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e23007 · Cited by 1
“The blood-brain barrier (BBB) disruption, DNA damage, oxidative stress, and the ensuing inflammatory response, altered neurotransmission, and hormone alterations are only a few of the many mechanistic hypotheses that have been investigated [5,6].”
Background
The serotonergic neurons derived from rhombomere 2 are localized in the median raphe and project to the dorsal pallium in zebrafish
Shibayama, K., Nakajo, H., Tanimoto, Y., Kakinuma, H., Shiraki, T., Tsuboi, T., & Okamoto, H. (2024) · Neuroscience Research · doi:10.1016/j.neures.2024.03.001 · Cited by 1
“In mammals, there are multiple subtypes of median raphe serotonergic neurons depending on the differences in gene expression and neural activity (Luchetti et al., 2020; Ren et al., 2019).”
Background
Dip2a regulates stress susceptibility in the basolateral amygdala
Li, J., He, Z., Chai, W., Tian, M., Yu, H., He, X., & Zhu, X. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-01871 · Cited by 1
“These datasets were previously published by Ren et al., (2019) and O’Leary et al. (2020), respectively.”
Monoamine Neurotransmission and Toxicity
Moyano, P. M., & Pino, J. D. (2024) · Royal Society of Chemistry eBooks · doi:10.1039/9781839165795-00255 · Cited by 1
Spatial differences in gene expression across the dorsal raphe nucleus in a model of early Alzheimer's disease
Kolling, L. J., Chimenti, M. S., & Marcinkiewcz, C. A. (2024) · Journal of Alzheimer s Disease · doi:10.1177/13872877241299119 · Cited by 1
“24,66,67 Visium clustering of the dorsal raphe nucleus is consistent with functionally-distinct subregions Others have found that the DRN is spatially organized into functionally-distinct subregions, 42,43,68 so we sought to determine a similar transcriptionally-de ﬁ ned organization.”
Acute Optogenetic Stimulation of Serotonin Neurons Reduces Cell Proliferation in the Dentate Gyrus of Mice
Araragi, N., Petermann, M., Mototaka Suzuki, A., Larkum, M. E., Mosienko, V., Bäder, M., Alenina, N. V., & Klempin, F. (2025) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.4c00771 · Cited by 1
The NonHuman Primate Neuroimaging & Neuroanatomy ProjectPreprint
Hayashi, T., Hou, Y., Glasser, M. F., Autio, J. A., Knoblauch, K., Inoue‐Murayama, M., Coalson, T., Yacoub, E. S., Smith, S. M., Kennedy, H., et al. (2020) · arXiv (Cornell University) · doi:10.48550/arxiv.2010.00308 · Cited by 2
“Ideally, this type of neuroimaging-based parcellation strategy would be combined with one based on postmortem architectonics, including cytoarchitecture, chemoarchitecture (Zilles and Amunts, 2009), cells (Murakami et al., 2018; Ren et al., 2019), gene expression (Shimogori et al.”
Method
Optogenetic activation of dorsal raphe serotonin neurons induces a brain-wide response in reward networkPreprint
Hamada, H. T., Abe, Y., Takata, N., Taira, M., Tanaka, K. F., & Doya, K. (2022) · Research Square · doi:10.21203/rs.3.rs-1958666/v1 · Cited by 1
A brain circuit and neuronal mechanism for decoding and adapting to change in daylengthPreprint
Maddaloni, G., Chang, Y., Senft, R., & Dymecki, S. M. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.11.557218 · Cited by 1
“Because serotonergic axons typically collateralize to multiple brain regions 33–35 , we explored the innervation profile specifically of the mr En1-Pet1 →SCN neuron subgroup.”
Qualitative Observations of Transgenically Individualized Serotonergic Fibers in the Mouse TelencephalonPreprint
Haiman, J. H., Mays, K. C., Roostaeyan, H. A., Elyasi, N., & Janušonis, S. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.25.568688 · Cited by 1
“They may instead reflect individually-specific transcriptome programs of the corresponding somata, 1,30,31 the individual age of the segments, 41 or their unique individual history (e.g., a certain appearance may be induced a physical obstacle resisting fiber extension and may persist for some time…”
Background
The gene expression landscape of the human locus coeruleus revealed by single-nucleus and spatially-resolved transcriptomicsPreprint
Weber, L. M., Divecha, H. R., Tran, M. N., Kwon, S. H., Spangler, A., Montgomery, K. D., Tippani, M., Bharadwaj, R. A., Kleinman, J. E., Page, S. C., et al. (2023) · eLife · doi:10.7554/elife.84628.2 · Cited by 1
Serotonin system development and adult function are regulated by GDNFPreprint
Garton, D. R., Runneberger, I., Casserly, L., Schorling, T., Montaño-Rodriguez, A., Iivananen, V., Kopra, J. J., Mätlik, K., Fagerström‐Billai, F., Damdimopoulos, A. E., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.11.627811 · Cited by 1
Shared Alteration of Whole-Brain Connectivity and Olfactory Deficits in Multiple Autism Mouse ModelsPreprint
Hsu, T., Chen, C.-P., Lin, M.-H., Huang, T., Wang, C.-Y., Lee, C.-M., Chen, B., Wang, C.-Y., & Hsueh, Y. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.02.636175 · Cited by 1
Hyperactivity of the Amygdala Mediates Depressive-Like Phenotypes and Decreased Serotonin ReleasePreprint
Kim, K., Lai, Y., Gao, Q., Wang, H., Ying, K. T., Asim, M., & He, J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.10.642393 · Cited by 1
“The dorsal raphe nucleus (DRN) is a primary source of serotonin (5-HT) and projects to various brain regions (Lesch & Waider, 2012; Ren et al., 2019).”
Concerted actions of distinct serotonin neurons orchestrate female pup care behaviorPreprint
Xiao, S. A., Chen, C. C., Horvath, P. M., Tsai, V. S., Cardenas, V. M., Biderman, D., Deng, F., Li, Y., Linderman, S. W., Dulac, C. G., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.31.667987 · Cited by 1
“Individual serotonin neurons often collateralize to multiple brain regions 18,19,46,47 .”
Self-citation
Hyperexcitability of female serotonin neurons underlies sex-specific anxiety responsesPreprint
Pizzoccaro, L., van der Veldt, S., Henderson, F. J., Simard, A.-S., Perreault, F., Fortin‐Houde, J., Lalot, E., Ducharme, G., & Amilhon, B. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.17.670715 · Cited by 3
Enhancer-AAVs allow genetic access to oligodendrocytes and diverse populations of astrocytes across speciesPreprint
Mich, J. K., Sunil, S., Johansen, N., Martinez, R. A., Liu, J., Gore, B. B., Mahoney, J. T., Leytze, M., Ben‐Simon, Y., Bertagnolli, D., et al. (2025) · eLife · doi:10.7554/elife.108640.1 · Cited by 1
Enhancer-AAVs allow genetic access to oligodendrocytes and diverse populations of astrocytes across speciesPreprint
Mich, J. K., Sunil, S., Johansen, N., Martinez, R. A., Liu, J., Gore, B. B., Mahoney, J. T., Leytze, M., Ben‐Simon, Y., Bertagnolli, D., et al. (2025) · eLife · doi:10.7554/elife.108640 · Cited by 1
Organization, development, and plasticity of the serotonergic dorsal raphe nucleus projectomePreprint
Jiménez-Fernández, L., Varga, Z. K., Thurner, K., & Kermen, F. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.03.04.709518 · Cited by 2
“In mice, a pioneer study leveraged genetic intersectional strategies to sparsely label and reconstruct the whole-brain projections of single serotonergic neurons 10 .”
Topographical Organization of M-Current on Dorsal and Median Raphe Serotonergic Neurons
Bayasgalan, T., Csemer, A., Kovács, A., Pocsai, K., & Pál, B. Z. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.614947
Cerebellar Circuitry of Tremor
Pan, M., & Kuo, S. (2021) · Contemporary clinical neuroscience · doi:10.1007/978-3-030-75817-2_27
Faculty Opinions recommendation of Mapping mesoscale axonal projections in the mouse brain using a 3D convolutional network.
Herrera, E., & Escalante, A. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.737865369.793579549
Serotonergic fast lane from taste detection to preparatory digestive actions
Wang, T., Pool, A., & Oka, Y. (2022) · Neuron · doi:10.1016/j.neuron.2022.02.023
Faculty Opinions recommendation of A genetically encoded sensor for measuring serotonin dynamics.
Knöpfel, T. (2021) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.739874841.793585307
Unbiased Intestinal Single Cell Transcriptomics Reveals Previously Uncharacterized Enteric Nervous System Populations in Larval ZebrafishPreprint
Kuil, L. E., Kakiailatu, N. J. M., Windster, J. D., Bindels, E. M., Zink, J., van der Zee, G., Hofstra, R. M. W., Shepherd, I. T., Melotte, V., & Alves, M. M. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4198508
eLife assessment: The gene expression landscape of the human locus coeruleus revealed by single-nucleus and spatially-resolved transcriptomics
Eisen, M. B. (2023) · eLife · doi:10.7554/elife.84628.1.sa4
Author Response: The gene expression landscape of the human locus coeruleus revealed by single-nucleus and spatially-resolved transcriptomics
Weber, L. M., Divecha, H. R., Tran, M. N., Kwon, S. H., Spangler, A., Montgomery, K. D., Tippani, M., Bharadwaj, R. A., Kleinman, J. E., Page, S. C., et al. (2023) · eLife · doi:10.7554/elife.84628.1.sa0
Reviewer #2 (Public Review): The gene expression landscape of the human locus coeruleus revealed by single-nucleus and spatially-resolved transcriptomics
(2023) · eLife · doi:10.7554/elife.84628.1.sa2
Reviewer #3 (Public Review): The gene expression landscape of the human locus coeruleus revealed by single-nucleus and spatially-resolved transcriptomics
(2023) · eLife · doi:10.7554/elife.84628.1.sa1
Reviewer #1 (Public Review): The gene expression landscape of the human locus coeruleus revealed by single-nucleus and spatially-resolved transcriptomics
(2023) · eLife · doi:10.7554/elife.84628.1.sa3
Rare CRHR2 and GRM8 variants identified as candidate factors associated with eating disorders in Japanese patientsPreprint
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Background
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Influential
Pre-Existing Serotonergic Pathways Guide the Navigation of Developing Serotonergic AxonsPreprint
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InfluentialSelf-citation
New projectome captures ‘complex beast’ of serotonin system in mice
Shaw, M. (2026) · The Transmitter · doi:10.53053/gmvm5223

Authors: Ren, J., Isakova, A., Friedmann, D., Zeng, J., Grutzner, S. M., Pun, A., Zhao, G. Q., Kolluru, S. S., Wang, R., Lin, R., Li, P., Li, A., Raymond, J. L., Luo, Q., Luo, M., Quake, S. R., & Luo, L.
Affiliations: Howard Hughes Medical Institute (US)
Stanford University (US)
National Institute of Biological Sciences, Beijing (CN)
Stanford Medicine (US)
Wuhan National Laboratory for Optoelectronics (CN)
Chan Zuckerberg Biohub San Francisco (US)
Corresponding author: Ren, Jing
Quake, Stephen R
Luo, Liqun
ORCID: Ren, Jing
Isakova, Alina
Friedmann, Drew
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
Venue: eLife
Publisher: eLife Sciences Publications, Ltd
Published: 2019-10-24
Volume: 8
ISSN: 2050-084X (ISSN-L)
DOI: 10.7554/elife.49424
PMC: PMC6812963
OpenAlex: W2982239238
Semantic Scholar: 73c6ef27934225685f1623abe2f5530230da5ad5
Cited by: 304
References: 97
Citations by year: 2026: 32 · 2025: 52 · 2024: 50 · 2023: 59 · 2022: 42 · 2021: 41 · 2020: 25 · 2019: 2
FWCI: 9.10
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
creativecommons.org/licenses/by/4.0/ (am)
creativecommons.org/licenses/by/4.0/ (tdm)
Locations: eLife (publishedVersion, cc-by)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institutes of Health (R01 NS104698, NS057488)
National Science Foundation (NeuroNex)
Ministry of Science and Technology of the People's Republic of China (2015BAI08B02)
National Natural Science Foundation of China (91432114, 91632302)
Beijing Municipal Government
NSFC (61721092, 81827901)
Swiss National Science Foundation (PostDoc Mobility Fellowship)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: serotonergic neurons, dorsal raphe nucleus, median raphe nucleus, single-cell transcriptomics, neuronal heterogeneity, VGLUT3, thyrotropin-releasing hormone, hypothalamus, neuropeptides, single-neuron reconstruction, mice
MeSH terms: Animals, Brain Mapping, Neural Pathways, Raphe Nuclei, Sequence Analysis, RNA, Mice, Single-Cell Analysis, Serotonergic Neurons, Transcriptome

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

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