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Mouse enteric neurons control intestinal plasmacytoid dendritic cell function via serotonin-HTR7 signaling [DC_5HT RNA-seq]

ABSTRACT: Serotonergic neurons have multiple roles, including regulating mood and behavior1,2, yet it remains unclear which of these phenotypes are caused by serotonin produced by the central versus the peripheral nervous system. Neuronal serotonin is produced by the enzyme tryptophan hydroxylase 2 (Tph2). Mice that lack Tph2 exhibit decreased gut motility4 and several behavioral disorders, including decreased anxiety-like behavior and increased aggression5. To clarify the specific role of peripheral serotonergic circuits, here we engineered mice with intact Tph2 in central neurons but lacking Tph2 in peripheral neurons (Tph2fl/fl; Hand2-Cre). We discovered that PSN contribute to gut motility and are important in the control of anxiety-like behavior but do not contribute to impulsive aggression. Thus, central and peripheral serotonergic neurons have different roles in behavioral regulation. Intriguingly, animals lacking peripheral neuronal Tph2 had deficiencies in enteric immune cells, including reduced abundance of dendritic cells (DC) and IgA+ B cells in the small intestine and elevated susceptibility to oral Salmonella infection. Mechanistic studies suggest that serotonin produced by PSN promotes activation of DC through the 5-HT7 receptor, thereby facilitating DC-mediated differentiation of IgA+ B cells. Our findings highlight the importance of serotonin produced by peripheral neurons for control of behavior and gut defense and suggest that these circuits could be valuable targets for therapeutics.

ORGANISM(S): Mus musculus

PROVIDER: GSE227125 | GEO | 2024/09/04

REPOSITORIES: GEO

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Mouse enteric neurons control intestinal plasmacytoid dendritic cell function via serotonin-HTR7 signaling [Cd45 RNAseq]

Project description:Serotonergic neurons have multiple roles, including regulating mood and behavior1,2, yet it remains unclear which of these phenotypes are caused by serotonin produced by the central versus the peripheral nervous system. Neuronal serotonin is produced by the enzyme tryptophan hydroxylase 2 (Tph2)3. Mice that lack Tph2 exhibit decreased gut motility4 and several behavioral disorders, including decreased anxiety-like behavior and increased aggression5. To clarify the specific role of peripheral serotonergic circuits, here we engineered mice with intact Tph2 in central neurons but lacking Tph2 in peripheral neurons (Tph2fl/fl; Hand2-Cre). We discovered that PSN contribute to gut motility and are important in the control of anxiety-like behavior but do not contribute to impulsive aggression. Thus, central and peripheral serotonergic neurons have different roles in behavioral regulation. Intriguingly, animals lacking peripheral neuronal Tph2 had deficiencies in enteric immune cells, including reduced abundance of dendritic cells (DC) and IgA+ B cells in the small intestine and elevated susceptibility to oral Salmonella infection. Mechanistic studies suggest that serotonin produced by PSN promotes activation of DC through the 5-HT7 receptor, thereby facilitating DC-mediated differentiation of IgA+ B cells. Our findings highlight the importance of serotonin produced by peripheral neurons for control of behavior and gut defense and suggest that these circuits could be valuable targets for therapeutics.

2024-09-04 | GSE227338 | GEO

Mouse enteric neurons control intestinal plasmacytoid dendritic cell function via serotonin-HTR7 signaling [16S]

2024-09-04 | GSE227333 | GEO

Mouse enteric neurons control intestinal plasmacytoid dendritic cell function via serotonin-HTR7 signaling [scRNA-seq]

Project description:Serotonergic neurons have multiple roles, including regulating mood and behavior1,2, yet it remains unclear which of these phenotypes are caused by serotonin produced by the central versus the peripheral nervous system. Neuronal serotonin is produced by the enzyme tryptophan hydroxylase 2 (Tph2). Mice that lack Tph2 exhibit decreased gut motility4 and several behavioral disorders, including decreased anxiety-like behavior and increased aggression5. To clarify the specific role of peripheral serotonergic circuits, here we engineered mice with intact Tph2 in central neurons but lacking Tph2 in peripheral neurons (Tph2fl/fl; Hand2-Cre). We discovered that PSN contribute to gut motility and are important in the control of anxiety-like behavior but do not contribute to impulsive aggression. Thus, central and peripheral serotonergic neurons have different roles in behavioral regulation. Intriguingly, animals lacking peripheral neuronal Tph2 had deficiencies in enteric immune cells, including reduced abundance of dendritic cells (DC) and IgA+ B cells in the small intestine and elevated susceptibility to oral Salmonella infection. Mechanistic studies suggest that serotonin produced by PSN promotes activation of DC through the 5-HT7 receptor, thereby facilitating DC-mediated differentiation of IgA+ B cells. Our findings highlight the importance of serotonin produced by peripheral neurons for control of behavior and gut defense and suggest that these circuits could be valuable targets for therapeutics.

2024-09-04 | GSE227217 | GEO

Mouse enteric neurons control intestinal plasmacytoid dendritic cell function via serotonin-HTR7 signaling [Sep_Epi]

Project description:Serotonergic neurons have multiple roles, including regulating mood and behavior1,2, yet it remains unclear which of these phenotypes are caused by serotonin produced by the central versus the peripheral nervous system. Neuronal serotonin is produced by the enzyme tryptophan hydroxylase 2 (Tph2). Mice that lack Tph2 exhibit decreased gut motility4 and several behavioral disorders, including decreased anxiety-like behavior and increased aggression5. To clarify the specific role of peripheral serotonergic circuits, here we engineered mice with intact Tph2 in central neurons but lacking Tph2 in peripheral neurons (Tph2fl/fl; Hand2-Cre). We discovered that PSN contribute to gut motility and are important in the control of anxiety-like behavior but do not contribute to impulsive aggression. Thus, central and peripheral serotonergic neurons have different roles in behavioral regulation. Intriguingly, animals lacking peripheral neuronal Tph2 had deficiencies in enteric immune cells, including reduced abundance of dendritic cells (DC) and IgA+ B cells in the small intestine and elevated susceptibility to oral Salmonella infection. Mechanistic studies suggest that serotonin produced by PSN promotes activation of DC through the 5-HT7 receptor, thereby facilitating DC-mediated differentiation of IgA+ B cells. Our findings highlight the importance of serotonin produced by peripheral neurons for control of behavior and gut defense and suggest that these circuits could be valuable targets for therapeutics.

2024-09-04 | GSE227216 | GEO

Mouse enteric neurons control intestinal plasmacytoid dendritic cell function via serotonin-HTR7 signaling [Co_Epi]

Project description:Serotonergic neurons have multiple roles, including regulating mood and behavior1,2, yet it remains unclear which of these phenotypes are caused by serotonin produced by the central versus the peripheral nervous system. Neuronal serotonin is produced by the enzyme tryptophan hydroxylase 2 (Tph2). Mice that lack Tph2 exhibit decreased gut motility4 and several behavioral disorders, including decreased anxiety-like behavior and increased aggression5. To clarify the specific role of peripheral serotonergic circuits, here we engineered mice with intact Tph2 in central neurons but lacking Tph2 in peripheral neurons (Tph2fl/fl; Hand2-Cre). We discovered that PSN contribute to gut motility and are important in the control of anxiety-like behavior but do not contribute to impulsive aggression. Thus, central and peripheral serotonergic neurons have different roles in behavioral regulation. Intriguingly, animals lacking peripheral neuronal Tph2 had deficiencies in enteric immune cells, including reduced abundance of dendritic cells (DC) and IgA+ B cells in the small intestine and elevated susceptibility to oral Salmonella infection. Mechanistic studies suggest that serotonin produced by PSN promotes activation of DC through the 5-HT7 receptor, thereby facilitating DC-mediated differentiation of IgA+ B cells. Our findings highlight the importance of serotonin produced by peripheral neurons for control of behavior and gut defense and suggest that these circuits could be valuable targets for therapeutics.

2024-09-04 | GSE227208 | GEO

Generation of a TPH2-EGFP reporter cell line for Purification and Monitoring of Human Serotonin neurons in vitro and in vivo

Project description:Generation of serotonin neurons (SNs) from human pluripotent stem cells (hPSCs) provides a promising platform to explore the mechanisms of serotonin-associated neuropsychiatric disorders. However, neural differentiation always yields heterogeneous cell populations, making it difficult to identify and purify SNs in vitro or track them in vivo following transplantation. Herein, we generated a TPH2-EGFP reporter hPSC line with insertion of EGFP into the endogenous tryptophan hydroxylase 2 (TPH2) locus using CRISPR-Cas9-mediated gene editing technology. This TPH2-reporter, which faithfully indicated TPH2 expression during differentiation, enabled us to obtain purified SNs for subsequent transcriptional analysis and study of pharmacological responses to antidepressants. In addition, the reporter system showed strong EGFP expression to indicate SNs, which enabled us to explore in vitro and ex vivo electrophysiological properties of SNs. In conclusion, this TPH2-EGFP reporter cell line might be of great significance for studies on human SN-related development and differentiation, drug screening, disease modeling, and cell replacement therapies.

2022-09-22 | GSE206341 | GEO

High-fidelity encoding of mechanostimuli by tactile food-sensing neurons requires an ensemble of ion channels

Project description:Dopaminergic neurons (expressing Pdat-1::mStrawberry) and serotonergic neurons (expressing Ptph-1::GFP) were purified from C. elegans embryos and larvae. We identified transcripts that were enriched in dopaminergic neurons compared to serotonin neurons.

2023-03-30 | GSE228099 | GEO

Expression data from mouse proprioceptive sensory neuron subclasses.

Project description:Proprioception relies on two main classes of proprioceptive sensory neurons (pSNs). These neurons innervate two distinct peripheral receptors in muscle, muscle spindles (MSs) or Golgi tendon organs (GTOs), and synapse onto different sets of spinal targets, but the molecular basis of their distinct pSN subtype identity remains unknown. We used microarray analysis to compare gene expression profiles between MS- and GTO- innervating proprioceptors. We generated transgenic mice in which MS and GTO pSNs are labelled with different fluorescent proteins (see de Nooij et al., 2015 for details). We used Fluorescent Activated Cell Sorting (FACS) to isolate the MS and GTO pSN subsets from dissociated DRG from p7-10 transgenic mice. Neurons from multiple FACS experiments were pooled into three samples each for the MS and GTO pSN subset.

2015-01-14 | E-GEOD-64941 | biostudies-arrayexpress

Altered serotonergic circuitry in SSRI-resistant major depressive disorder patient-derived neurons

Project description:The goals of this study are to generate and study serotonergic neurons from MDD patients that are selective serotonin reuptake inhibitor (SSRI) remitters and SSRI-nonremitters (NR).

2022-02-12 | GSE126512 | GEO

Extraction of Total RNA from Single Neurons: Mauthner-cell Cytoplasm vs. Whole Brain

Project description:Astatotilapia burtoni males change their startle behavior in accordance with changes in a socially-mediated phenotypic state. When dominant (DOM), males are brightly colored, isolated from the school and startle readily in response to an auditory pulse. When subordinate (SUB), males are cryptically colored, school and startle less frequently. We hypothesize that the difference in startle responsiveness is governed by serotonergic modulation on the command-like Mauthner cells (M-cells). We used the selective serotonin receptor subtype 2 (5HTR2) antagonist ketanserin to show that serotonin receptors can modulate startle frequency and that the behavioral difference correlates with differences in electrophysiological recordings of M-cells. Specifically, SUB males have a higher serotonergic tone and demonstrate, by behavior and electrophysiological properties, increased sensitivity to 5-HT manipulations compared to DOMs. Immunohistochemistry for serotonin is present around the M-cells. Furthermore, we identified serotonin receptor transcripts in A. burtoni and used single-cell transcriptomics to determine the presence or absence of specific receptor subtypes in the M-cells. Microarray analysis of M-cell samples shows that the neuron’s transcriptome is relatively stable in individuals of different social status. These results are consistent with a role for serotonin in modulating the behavioral response to sensory stimuli in an ecologically-relevant manner through inhibitory interneurons, which establish the membrane resistance of the M-cell before the auditory stimulus. Simple loop with dye-swap containing 6 arrays from 2 sources with 3 biological replicates per source (3 M-cell and 3 whole brain samples).

2010-12-23 | E-GEOD-26277 | biostudies-arrayexpress

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