ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Mice with compromised 5-HTT function lack phosphotyrosine-mediated inhibitory control over prefrontal 5-HT responses.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Insomnia Pathogenesis and Multidimensional Mechanisms of Acupuncture: A Narrative Review.International journal of general medicine · 2026Review
- Research on a New Intelligent and Rapid Screening Method for Depression Risk in Young People Based on Eye Tracking Technology.Brain sciences · 2023Article
- A novel murine model of mania.Molecular psychiatry · 2023Article
- Src Family Kinases in the Central Nervous System: Their Emerging Role in Pathophysiology of Migraine and Neuropathic Pain.Current neuropharmacology · 2021Article
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Upregulated 5-HTMolecular brain · 2020Article
- Mapping the physiological and molecular markers of stress and SSRI antidepressant treatment in S100a10 corticostriatal neurons.Molecular psychiatry · 2020Article
- Ethanol Dependence Abolishes Monoamine and GIRK (Kir3) Channel Inhibition of Orbitofrontal Cortex Excitability.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
- Refining the Role of 5-HT in Postnatal Development of Brain Circuits.Frontiers in cellular neuroscience · 2017Review
- Enhanced 5-HT1A receptor-dependent feedback control over dorsal raphe serotonin neurons in the SERT knockout mouse.Neuropharmacology · 2015Article
- Postnatal day 2 to 11 constitutes a 5-HT-sensitive period impacting adult mPFC function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The activity of the prefrontal cortex is essential for normal emotional processing and is strongly modulated by serotonin (5-HT). Yet, little is known about the regulatory mechanisms that control the activity of the prefrontal 5-HT receptors. Here, we found and characterized a deregulation of prefrontal 5-HT receptor electrophysiological signaling in mouse models of disrupted serotonin transporter (5-HTT) function, a risk factor for emotional and cognitive disturbances. We identified a novel tyrosine kinase-dependent mechanism that regulates 5-HT-mediated inhibition of prefrontal pyramidal neurons. We report that mice with compromised 5-HTT, resulting from either genetic deletion or brief treatment with selective serotonin reuptake inhibitors during development, have amplified 5-HT1A receptor-mediated currents in adulthood. These greater inhibitory effects of 5-HT are accompanied by enhanced downstream coupling to Kir3 channels. Notably, in normal wild-type mice, we found that these larger 5-HT1A responses can be mimicked through inhibition of Src family tyrosine kinases. By comparison, in our 5-HTT mouse models, the larger 5-HT1A responses were rapidly reduced through inhibition of tyrosine phosphatases. Our findings implicate tyrosine phosphorylation in regulating the electrophysiological effects of prefrontal 5-HT1A receptors with implications for neuropsychiatric diseases associated with emotional dysfunction, such as anxiety and depressive disorders.
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Registered trials
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