Serotonin receptor 4 in the hippocampus modulates mood and anxiety
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA662219 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12606600_1.fastq.gz | Fastqsanger.gz | |||
| SRR12606600_2.fastq.gz | Fastqsanger.gz | |||
| SRR12606586_1.fastq.gz | Fastqsanger.gz | |||
| SRR12606586_2.fastq.gz | Fastqsanger.gz | |||
| SRR12606587_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 30 |
Similar Datasets
Project description:Serotonin receptor 4 (5‑HT4R) plays an important role in regulating mood, anxiety, and cognition, and drugs that activate this receptor have fast-acting antidepressant (AD)-like effects in preclinical models. However, 5‑HT4R is widely expressed throughout the central nervous system (CNS) and periphery, making it difficult to pinpoint the cell types and circuits underlying its effects. Therefore, we generated a Cre-dependent 5‑HT4R knockout mouse line to dissect the function of 5‑HT4R in specific brain regions and cell types. We show that the loss of functional 5‑HT4R specifically from excitatory neurons of hippocampus led to robust AD-like behavioral responses and an elevation in baseline anxiety. 5‑HT4R was necessary to maintain the proper excitability of dentate gyrus (DG) granule cells and cell type specific molecular profiling revealed a dysregulation of genes necessary for normal neural function and plasticity in cells lacking 5‑HT4R. These adaptations were accompanied by an increase in the number of immature neurons in ventral, but not dorsal, dentate gyrus, indicating a broad impact of 5‑HT4R loss on the local cellular environment. This study is the first to use conditional genetic targeting to demonstrate a direct role for hippocampal 5‑HT4R signaling in modulating mood and anxiety. Our findings also underscore the need for cell type-based approaches to elucidate the complex action of neuromodulatory systems on distinct neural circuits.
2021-01-08 | GSE157607 | GEO
Project description:Serotonin receptor 4 (5-HT4R) plays an important role in regulating mood, anxiety, and cognition, and drugs that activate this receptor have fast-acting antidepressant (AD)-like effects in preclinical models. However, 5-HT4R is widely expressed throughout the central nervous system (CNS) and periphery, making it difficult to pinpoint the cell types and circuits underlying its effects. Therefore, we generated a Cre-dependent 5-HT4R knockout mouse line to dissect the function of 5-HT4R in specific brain regions and cell types. We show that the loss of functional 5-HT4R specifically from excitatory neurons of hippocampus led to robust AD-like behavioral responses and an elevation in baseline anxiety. 5-HT4R was necessary to maintain the proper excitability of dentate gyrus (DG) granule cells and cell type-specific molecular profiling revealed a dysregulation of genes necessary for normal neural function and plasticity in cells lacking 5-HT4R. These adaptations were accompanied by an increase in the number of immature neurons in ventral, but not dorsal, dentate gyrus, indicating a broad impact of 5-HT4R loss on the local cellular environment. This study is the first to use conditional genetic targeting to demonstrate a direct role for hippocampal 5-HT4R signaling in modulating mood and anxiety. Our findings also underscore the need for cell type-based approaches to elucidate the complex action of neuromodulatory systems on distinct neural circuits.
| S-EPMC8275670 | biostudies-literature
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
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
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 | GSE227333 | GEO
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
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
Project description:A central extended amygdala circuit that modulates anxiety
| PRJNA454720 | ENA
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 | GSE227125 | GEO
Project description:The serotonin neurotransmitter modulates virulence of enteric pathogens
| PRJNA604962 | ENA