GABAergic and glutamatergic inputs to the medulla oblongata and locus coeruleus noradrenergic pathways are critical for seizures and postictal antinociception neuromodulation
Abstract We investigated the participation of the nucleus of the tractus solitarius (NTS) in tonic‒clonic seizures and postictal antinociception control mediated by NMDA receptors, the role of NTS GABAergic interneurons and noradrenergic pathways from the locus coeruleus (LC) in these phenomena. The...
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Nature Portfolio
2024-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-53744-3 |
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| author | Marcelo Mendonça-dos-Santos Thaís Cristina Teixeira Gonçalves Luiz Luciano Falconi-Sobrinho Tayllon dos Anjos-Garcia Ivair Matias Rithiele Cristina de Oliveira Maria de Fátima dos Santos Sampaio Fabrízio dos Santos Cardoso Wagner Ferreira dos Santos Helio Rubens Machado Norberto Cysne Coimbra |
| author_facet | Marcelo Mendonça-dos-Santos Thaís Cristina Teixeira Gonçalves Luiz Luciano Falconi-Sobrinho Tayllon dos Anjos-Garcia Ivair Matias Rithiele Cristina de Oliveira Maria de Fátima dos Santos Sampaio Fabrízio dos Santos Cardoso Wagner Ferreira dos Santos Helio Rubens Machado Norberto Cysne Coimbra |
| author_sort | Marcelo Mendonça-dos-Santos |
| collection | DOAJ |
| description | Abstract We investigated the participation of the nucleus of the tractus solitarius (NTS) in tonic‒clonic seizures and postictal antinociception control mediated by NMDA receptors, the role of NTS GABAergic interneurons and noradrenergic pathways from the locus coeruleus (LC) in these phenomena. The NTS-lateral nucleus reticularis paragigantocellularis (lPGi)-LC pathway was studied by evaluating neural tract tracer deposits in the lPGi. NMDA and GABAergic receptors agonists and antagonists were microinjected into the NTS, followed by pharmacologically induced seizures. The effects of LC neurotoxic lesions caused by DSP-4, followed by NTS-NMDA receptor activation, on both tonic‒clonic seizures and postictal antinociception were also investigated. The NTS is connected to lPGi neurons that send outputs to the LC. Glutamatergic vesicles were found on dendrites and perikarya of GABAergic interneurons in the NTS. Both tonic‒clonic seizures and postictal antinociception are partially dependent on glutamatergic-mediated neurotransmission in the NTS of seizing rats in addition to the integrity of the noradrenergic system since NMDA receptor blockade in the NTS and intrathecal administration of DSP-4 decrease the postictal antinociception. The GABAA receptor activation in the NTS decreases both seizure severity and postictal antinociception. These findings suggest that glutamatergic inputs to NTS-GABAergic interneurons, in addition to ascending and descending noradrenergic pathways from the LC, are critical for the control of both seizures and postictal antinociception. |
| first_indexed | 2024-03-07T15:09:12Z |
| format | Article |
| id | doaj.art-7dc2ea1ea00d4199b03d09f98621a731 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:09:12Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-7dc2ea1ea00d4199b03d09f98621a7312024-03-05T18:46:38ZengNature PortfolioScientific Reports2045-23222024-02-0114111710.1038/s41598-024-53744-3GABAergic and glutamatergic inputs to the medulla oblongata and locus coeruleus noradrenergic pathways are critical for seizures and postictal antinociception neuromodulationMarcelo Mendonça-dos-Santos0Thaís Cristina Teixeira Gonçalves1Luiz Luciano Falconi-Sobrinho2Tayllon dos Anjos-Garcia3Ivair Matias4Rithiele Cristina de Oliveira5Maria de Fátima dos Santos Sampaio6Fabrízio dos Santos Cardoso7Wagner Ferreira dos Santos8Helio Rubens Machado9Norberto Cysne Coimbra10Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP)Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP)Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP)Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP)Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP)Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP)Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP)Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP)Neurobiology and Venoms Laboratory, Department of Biology, Ribeirão Preto School of Philosophy, Sciences and Literature of the University of São Paulo (FFCLRP-USP)Laboratory of Paediatric Neurosurgery and Developmental Neuropathology, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São PauloLaboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP)Abstract We investigated the participation of the nucleus of the tractus solitarius (NTS) in tonic‒clonic seizures and postictal antinociception control mediated by NMDA receptors, the role of NTS GABAergic interneurons and noradrenergic pathways from the locus coeruleus (LC) in these phenomena. The NTS-lateral nucleus reticularis paragigantocellularis (lPGi)-LC pathway was studied by evaluating neural tract tracer deposits in the lPGi. NMDA and GABAergic receptors agonists and antagonists were microinjected into the NTS, followed by pharmacologically induced seizures. The effects of LC neurotoxic lesions caused by DSP-4, followed by NTS-NMDA receptor activation, on both tonic‒clonic seizures and postictal antinociception were also investigated. The NTS is connected to lPGi neurons that send outputs to the LC. Glutamatergic vesicles were found on dendrites and perikarya of GABAergic interneurons in the NTS. Both tonic‒clonic seizures and postictal antinociception are partially dependent on glutamatergic-mediated neurotransmission in the NTS of seizing rats in addition to the integrity of the noradrenergic system since NMDA receptor blockade in the NTS and intrathecal administration of DSP-4 decrease the postictal antinociception. The GABAA receptor activation in the NTS decreases both seizure severity and postictal antinociception. These findings suggest that glutamatergic inputs to NTS-GABAergic interneurons, in addition to ascending and descending noradrenergic pathways from the LC, are critical for the control of both seizures and postictal antinociception.https://doi.org/10.1038/s41598-024-53744-3Refractory epilepsyTonic‒clonic seizuresNucleus of the tractus solitariusNMDA receptorGABAA receptorLocus coeruleus |
| spellingShingle | Marcelo Mendonça-dos-Santos Thaís Cristina Teixeira Gonçalves Luiz Luciano Falconi-Sobrinho Tayllon dos Anjos-Garcia Ivair Matias Rithiele Cristina de Oliveira Maria de Fátima dos Santos Sampaio Fabrízio dos Santos Cardoso Wagner Ferreira dos Santos Helio Rubens Machado Norberto Cysne Coimbra GABAergic and glutamatergic inputs to the medulla oblongata and locus coeruleus noradrenergic pathways are critical for seizures and postictal antinociception neuromodulation Scientific Reports Refractory epilepsy Tonic‒clonic seizures Nucleus of the tractus solitarius NMDA receptor GABAA receptor Locus coeruleus |
| title | GABAergic and glutamatergic inputs to the medulla oblongata and locus coeruleus noradrenergic pathways are critical for seizures and postictal antinociception neuromodulation |
| title_full | GABAergic and glutamatergic inputs to the medulla oblongata and locus coeruleus noradrenergic pathways are critical for seizures and postictal antinociception neuromodulation |
| title_fullStr | GABAergic and glutamatergic inputs to the medulla oblongata and locus coeruleus noradrenergic pathways are critical for seizures and postictal antinociception neuromodulation |
| title_full_unstemmed | GABAergic and glutamatergic inputs to the medulla oblongata and locus coeruleus noradrenergic pathways are critical for seizures and postictal antinociception neuromodulation |
| title_short | GABAergic and glutamatergic inputs to the medulla oblongata and locus coeruleus noradrenergic pathways are critical for seizures and postictal antinociception neuromodulation |
| title_sort | gabaergic and glutamatergic inputs to the medulla oblongata and locus coeruleus noradrenergic pathways are critical for seizures and postictal antinociception neuromodulation |
| topic | Refractory epilepsy Tonic‒clonic seizures Nucleus of the tractus solitarius NMDA receptor GABAA receptor Locus coeruleus |
| url | https://doi.org/10.1038/s41598-024-53744-3 |
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