Thalamic distribution and effects of 5-HT2C receptors on tonic GABAA inhibition and absence seizures: implications for treatment
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Le résumé fourni par la source
Introduction Childhood absence epilepsy (CAE) is associated with abnormal thalamocortical oscillations and enhanced GABAergic function in the ventrobasal (VB) thalamus, including increased extrasynaptic GABA A receptor–mediated tonic currents in thalamocortical (TC) neurons. Serotonin signaling modulates seizure activity in several epilepsy models, and activation of 5-HT 2C receptors (5-HT 2C Rs) has been reported to exert anti-absence seizure effects, although the underlying cellular mechanisms remain unclear. Here, we examined the thalamic distribution of 5-HT 2C Rs and their functional impact on tonic GABAA inhibition and absence seizures. Methods 5-HT 2C R expression in the nucleus reticularis thalami (NRT) and VB was assessed by immunohistochemistry in adult Wistar rats, Genetic Absence Epilepsy Rats from Strasbourg (GAERS), and their non-epileptic control strain (NEC). Whole-cell patch-clamp recordings were used to measure tonic GABAA currents in VB TC neurons in thalamic slices. In vivo EEG recordings in freely moving GAERS rats were performed to evaluate the effects of systemic administration of the 5-HT2CR agonist Ro 60-0175 on absence seizures. Results No differences in 5-HT 2C R expression were observed in the NRT across strains. In the VB, receptor expression was lowest in GAERS and highest in Wistar rats compared with NEC. Tonic GABAA currents in TC neurons were larger in GAERS than in Wistar or NEC rats. Activation of 5-HT 2C Rs with Ro 60-0175 reduced tonic GABAA currents in TC neurons in all strains. Systemic administration of Ro 60-0175 in adult GAERS produced a clear reduction in absence seizures. Discussion These findings indicate that 5-HT 2C Rs regulate thalamic extrasynaptic GABAA inhibition and that their activation reduces tonic inhibitory drive in TC neurons while exerting anti-absence effects in vivo. The lower expression of 5-HT 2C Rs in the GAERS VB suggests altered serotonergic control of thalamic inhibition in absence epilepsy. By reducing tonic GABAergic currents, 5-HT 2C R activation may rebalance thalamocortical activity and suppress pathological oscillations, supporting these receptors as potential therapeutic targets for CAE.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Thalamic distribution and effects of 5-HT2C receptors on tonic GABAA inhibition and absence seizures: implications for treatment
- Date Crossref
- 20/02/2026
- Éditeur
- Frontiers Media SA
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Zurich Laboratory of Neural Circuit Assembly pays non établi dans la noticeUniversité ou école supérieure
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Cardiff University pays non établi dans la noticeUniversité ou école supérieure
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University of Bologna Department of Veterinary Medical Science pays non établi dans la noticeUniversité ou école supérieure
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University of Lisbon pays non établi dans la noticeUniversité ou école supérieure
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Institute of Pharmacology pays non établi dans la noticeStructure de recherche
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Korea University pays non établi dans la noticeUniversité ou école supérieure
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Magna Graecia University pays non établi dans la noticeUniversité ou école supérieure
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School of Bioscience Neuroscience Division pays non établi dans la noticeUniversité ou école supérieure
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Faculty of Medicine Institute of Pharmacology and Neurosciences pays non établi dans la noticeUniversité ou école supérieure
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College of Medicine pays non établi dans la noticeUniversité ou école supérieure
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University of Magna Graecia Department of Medical and Surgical Sciences pays non établi dans la noticeUniversité ou école supérieure
Laboratory of Neural Circuit Assembly — University of Zurich, Cardiff University et Department of Veterinary Medical Science — University of Bologna, avec 8 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.