ArticleThe Journal of physiology2008
Serotonin facilitates long-term depression induction in prefrontal cortex via p38 MAPK/Rab5-mediated enhancement of AMPA receptor internalization.
Article in The Journal of physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- Identification of 22q13 genes most likely to contribute to Phelan McDermid syndrome.European journal of human genetics : EJHG · 2018Pooled it
- The Molecular Machinery of Synaptic Plasticity and Its Potential Role in the Aetiology of Schizophrenia.Molecular neurobiology · 2026Review
- Serotonin-endocannabinoid crosstalk selectively regulates inhibitory GABAergic inputs in the medial prefrontal cortex.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- PKMζ is necessary for long-term depression and long-term potentiation in the medial prefrontal cortex.The Journal of physiology · 2026Article
- Impact of distinct neurotransmitter release modes on neuronal signaling.Molecular psychiatry · 2026Review
- Prolonged visual experience accelerates developmental synaptic downscaling via epigenetic regulation and Rab5c mediated AMPA receptor trafficking.Communications biology · 2026Article
- Neuroprotective actions of norepinephrine in neurological diseases.Pflugers Archiv : European journal of physiology · 2024Review
- Multiple modulatory roles of serotonin in chronic pain and injury-related anxiety.Frontiers in synaptic neuroscience · 2023Review
- Review
- Serotonin facilitates late-associative plasticity via synaptic tagging/cross-tagging and capture at hippocampal CA2 synapses in male rats.Oxford open neuroscience · 2022Article
- Long-term memory, synaptic plasticity and dopamine in rodent medial prefrontal cortex: Role in executive functions.Frontiers in behavioral neuroscience · 2022Review
- Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications.Molecular psychiatry · 2022Review
- Identification of Potential Biomarkers of Depression and Network Pharmacology Approach to Investigate the Mechanism of Key Genes and Therapeutic Traditional Chinese Medicine in the Treatment of Depression.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Layer-specific serotonergic induction of long-term depression in the prefrontal cortex of rats.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2020Article
- P38α MAPK Signaling-A Robust Therapeutic Target for Rab5-Mediated Neurodegenerative Disease.International journal of molecular sciences · 2020Review
- Coordination of AMPA receptor trafficking by Rab GTPases.Small GTPases · 2019Review
- Neuromodulators and Long-Term Synaptic Plasticity in Learning and Memory: A Steered-Glutamatergic Perspective.Brain sciences · 2019Review
- Neural circuits for a top-down control of fear and extinction.Psychopharmacology · 2019Review
- Metabotropic Glutamate Receptor 5 in the Medial Prefrontal Cortex as a Molecular Determinant of Pain and Ensuing Depression.Frontiers in molecular neuroscience · 2018Article
- Role of mGluACS chemical neuroscience · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The serotonin system in prefrontal cortex (PFC) is critically involved in the regulation of cognition and emotion. To understand the cellular mechanisms underlying its physiological actions, we investigated the role of serotonin in regulating synaptic plasticity in PFC circuits. We found that tetanic stimuli coupled to bath application of serotonin induced long-term depression (LTD) at excitatory synapses of PFC pyramidal neurons. This effect was mediated by 5-HT(2A/C) receptors and was independent of NMDA receptor activation. A group I metabotropic glutamate receptor (mGluR) antagonist blocked the LTD induction by serotonin + tetani, and co-application of a group I mGluR agonist and serotonin, but not application of either drug alone, induced LTD without tetani. The effect of serotonin on LTD was blocked by selective inhibitors of p38 mitogen-activated protein kinase (MAPK), but not p42/44 MAPK. Biochemical evidence also indicated that serotonin and a group I mGluR agonist synergistically activated p38 MAPK in PFC slices. The serotonin-facilitated LTD induction was prevented by blocking the activation of the small GTPase Rab5, as well as by blocking the clathrin-dependent internalization of AMPA receptors with postsynaptic injection of a dynamin inhibitory peptide, while it was unaffected by manipulating the cytoskeleton. Interestingly, in animals exposed to acute stress, the LTD induction by serotonin + tetani was significantly impaired. Taken together, these results suggest that serotonin, by cooperating with mGluRs, regulates synaptic plasticity through a mechanism dependent on p38 MAPK/Rab5-mediated enhancement of AMPA receptor internalization in a clathrin/dynamin-dependent manner. It provides a potential mechanism underlying the role of serotonin in controlling emotional and cognitive processes that are mediated by synaptic plasticity in PFC neurons.
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