ArticleTranslational psychiatry2012
Serotonin 1A receptor-mediated signaling through ERK and PKCα is essential for normal synaptogenesis in neonatal mouse hippocampus.
Article in Translational psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 69 citations in OpenAlex.
- Chronic Hyponatremia Potentiates Innate Anxiety-Like Behaviors Through the Dysfunction of Monoaminergic Neurons in Mice.Molecular neurobiology · 2025Article
- Circuit Reconstruction after Traumatic Spinal Cord Injury by Cellular and Pharmacological Approaches.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Hereditary Patterns and Genetic Associations in Obsessive-Compulsive Disorder (OCD): Neuropsychiatric Insights, Genetic Influences, and Treatment Perspectives.Current gene therapy · 2025Review
- Spinal motoneurons respond aberrantly to serotonin in a rabbit model of cerebral palsy.The Journal of physiology · 2023Article
- PET imaging of animal models with depressive-like phenotypes.European journal of nuclear medicine and molecular imaging · 2023Review
- Spinal motoneurons respond aberrantly to serotonin in a rabbit model of cerebral palsy.bioRxiv : the preprint server for biology · 2023Article
- Serotonin Receptors as Therapeutic Targets for Autism Spectrum Disorder Treatment.International journal of molecular sciences · 2022Review
- The role of serotonin neurotransmission in rapid antidepressant actions.Psychopharmacology · 2022Review
- The G Protein-Coupled Serotonin 1A Receptor Augments Protein Kinase Cε-Mediated Neurogenesis in Neonatal Mouse Hippocampus-PKCε-Mediated Signaling in the Early Hippocampus.International journal of molecular sciences · 2022Article
- The roles of serotonin in cell adhesion and migration, and cytoskeletal remodeling.Cell adhesion & migration · 2021Review
- The epigenetic role of HTR1A antagonist in facilitaing GnRH expression for pubertal initiation control.Molecular therapy. Nucleic acids · 2021Article
- Modulation of Serotonin Receptors in Neurodevelopmental Disorders: Focus on 5-HT7 Receptor.Molecules (Basel, Switzerland) · 2021Review
- Rewiring of the Serotonin System in Major Depression.Frontiers in psychiatry · 2021Review
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- MAP/ERK Signaling in Developing Cognitive and Emotional Function and Its Effect on Pathological and Neurodegenerative Processes.International journal of molecular sciences · 2020Review
- Altered Motoneuron Properties Contribute to Motor Deficits in a Rabbit Hypoxia-Ischemia Model of Cerebral Palsy.Frontiers in cellular neuroscience · 2020Article
- Functional Interrogation of a Depression-Related Serotonergic Single Nucleotide Polymorphism, rs6295, Using a Humanized Mouse Model.ACS chemical neuroscience · 2019Article
- Genetic, epigenetic and posttranscriptional mechanisms for treatment of major depression: the 5-HT1A receptor gene as a paradigmJournal of psychiatry & neuroscience : JPN · 2019Review
- Targeting Serotonin1A Receptors for Treating Chronic Pain and Depression.Current neuropharmacology · 2019Review
- Overcoming Resistance to Selective Serotonin Reuptake Inhibitors: Targeting Serotonin, Serotonin-1A Receptors and Adult Neuroplasticity.Frontiers in neuroscience · 2019Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Aberrant expression of the presynaptic serotonin 1A receptor (5-HT(1A)-R) because of a polymorphism in the 5-HT(1A)-R gene is associated with severe depression in human, whereas its absence up to postnatal day 21 (P21) in the forebrain of mice results in heightened anxiety in adulthood. These observations collectively indicate that the 5-HT(1A)-R has a crucial role in brain development. To understand the mechanistic underpinnings of this phenomenon, we used organotypic slice cultures of hippocampi from C57BL6 mice (C57) at P15, which coincides with the peak of neonatal synaptogenesis. Stimulation of the hippocampal 5-HT(1A)-R caused a dramatic increase in PSD95 expression and dendritic spine and synapse formation through sequential activation of the mitogen-activated protein kinase isozymes Erk1/2 and protein kinase C (PKC). Intrahippocampal infusion of 5-HT(1A)-R agonists and signaling inhibitors at P15 revealed that the same pathway through PKCα augments PSD95 expression and synaptogenesis in vivo in 24 h in both C57 as well as Swiss Webster mice. Furthermore, intrahippocampal infusion of the antidepressant fluoxetine, a serotonin reuptake inhibitor, also augmented PSD95 expression and synaptogenesis through the same pathway. This increased synaptogenesis was observed even 5 days after treatment. Finally, compared with the wild type, the 5-HT(1A)-R(-/-) mice harbor significantly less synapses in the hippocampus, but infusion of the PKC-stimulator and Alzheimer drug bryostatin into the 5-HT(1A)-R(-/-) mice to bypass the non-existent 5-HT(1A)-R boosted PSD95 expression and synaptogenesis. The elucidated signaling cascade explains how 5-HT(1A)-R regulates hippocampal sculpting and function, which may determine the affective phenotype of an adult.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.