ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Serotonin 5-HT1A receptors regulate NMDA receptor channels through a microtubule-dependent mechanism.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.
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Who cites it
102 citing papers in PubMed, 1 synthesis or guideline pooled it, 219 citations in OpenAlex.
- Convergent Neuroimaging and Molecular Signatures in Mild Cognitive Impairment and Alzheimer's Disease: A Data-Driven Meta-Analysis with N = 3,118.Neuroscience bulletin · 2024Pooled it
- Selective serotonin reuptake inhibition modulates response inhibition in Parkinson's disease.Brain : a journal of neurology · 2014Trial
- Serotonergic modulation of excitatory synapse development and plasticity.Molecules and cells · 2026Review
- Serotonin reuptake inhibiting antidepressants: A trigger for visual snow syndrome?The International journal of risk & safety in medicine · 2026Article
- Chronic Co-administration of Methylphenidate and Fluoxetine Reduces Striatal NMDA Receptor Binding in Adolescent Rats.Neurochemical research · 2026Article
- Mapping neurophysiological and molecular profiles of heterogeneity and homogeneity in schizophrenia-bipolar disorder.Science advances · 2025Article
- Serotonin Modulation of Dorsoventral Hippocampus in Physiology and Schizophrenia.International journal of molecular sciences · 2025Review
- Mechanisms of glutamate receptors hypofunction dependent synaptic transmission impairment in the hippocampus of schizophrenia susceptibility gene Opcml-deficient mouse model.Molecular brain · 2024Article
- Advances in the Treatment of Cognitive Impairment in Schizophrenia: Targeting NMDA Receptor Pathways.International journal of molecular sciences · 2024Review
- Prenatal risk factors and genetic causes of ADHD in children.World journal of pediatrics : WJP · 2022Review
- Novel probiotic treatment of autism spectrum disorder associated social behavioral symptoms in two rodent models.Scientific reports · 2022Article
- Review
- Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications.Molecular psychiatry · 2022Review
- Investigation of the Role of Stimulation and Blockade of 5-HTJournal of molecular neuroscience : MN · 2021Article
- Repetitive optogenetic stimulation of glutamatergic neurons: An alternative to NMDA treatment for generating locomotor activity in spinalized zebrafish larvae.Physiological reports · 2021Article
- Modulation of NMDA Receptors by G-protein-coupled receptors: Role in Synaptic Transmission, Plasticity and Beyond.Neuroscience · 2021Review
- Rewiring of the Serotonin System in Major Depression.Frontiers in psychiatry · 2021Review
- Upregulated 5-HTMolecular brain · 2020Article
- Changes in Serotonin Modulation of Glutamate Currents in Pyramidal Offspring Cells of Rats Treated With 5-MT during Gestation.Brain sciences · 2020Article
- An integrative analysis of 5HTT-mediated mechanism of hyperactivity to non-threatening voices.Communications biology · 2020Article
42 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The serotonin system and NMDA receptors (NMDARs) in prefrontal cortex (PFC) are both critically involved in the regulation of cognition and emotion under normal and pathological conditions; however, the interactions between them are essentially unknown. Here we show that serotonin, by activating 5-HT(1A) receptors, inhibited NMDA receptor-mediated ionic and synaptic currents in PFC pyramidal neurons, and the NR2B subunit-containing NMDA receptor is the primary target of 5-HT(1A) receptors. This effect of 5-HT(1A) receptors was blocked by agents that interfere with microtubule assembly, as well as by cellular knock-down of the kinesin motor protein KIF17 (kinesin superfamily member 17), which transports NR2B-containing vesicles along microtubule in neuronal dendrites. Inhibition of either CaMKII (calcium/calmodulin-dependent kinase II) or MEK/ERK (mitogen-activated protein kinase kinase/extracellular signal-regulated kinase) abolished the 5-HT(1A) modulation of NMDAR currents. Biochemical evidence also indicates that 5-HT(1A) activation reduced microtubule stability, which was abolished by CaMKII or MEK inhibitors. Moreover, immunocytochemical studies show that 5-HT(1A) activation decreased the number of surface NR2B subunits on dendrites, which was prevented by the microtubule stabilizer. Together, these results suggest that serotonin suppresses NMDAR function through a mechanism dependent on microtubule/kinesin-based dendritic transport of NMDA receptors that is regulated by CaMKII and ERK signaling pathways. The 5-HT(1A)-NMDAR interaction provides a potential mechanism underlying the role of serotonin in controlling emotional and cognitive processes subserved by PFC.
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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.