Modulation of GABAergic Synaptic Transmission by NMDA Receptors in the Dorsal Horn of the Spinal Cord
The dorsal horn (DH) of the spinal cord is an important structure involved in the integration of nociceptive messages. Plastic changes in the properties of neuronal networks in the DH underlie the development of analgesia as well as of hyperalgesia and allodynia in acute and chronic pain states. Two...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.903087/full |
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| author | Benjamin Leonardon Benjamin Leonardon Lou Cathenaut Lou Cathenaut Louise Vial-Markiewicz Louise Vial-Markiewicz Sylvain Hugel Rémy Schlichter Rémy Schlichter Perrine Inquimbert Perrine Inquimbert |
| author_facet | Benjamin Leonardon Benjamin Leonardon Lou Cathenaut Lou Cathenaut Louise Vial-Markiewicz Louise Vial-Markiewicz Sylvain Hugel Rémy Schlichter Rémy Schlichter Perrine Inquimbert Perrine Inquimbert |
| author_sort | Benjamin Leonardon |
| collection | DOAJ |
| description | The dorsal horn (DH) of the spinal cord is an important structure involved in the integration of nociceptive messages. Plastic changes in the properties of neuronal networks in the DH underlie the development of analgesia as well as of hyperalgesia and allodynia in acute and chronic pain states. Two key mechanisms are involved in these chronic pain states: increased electrical activities and glutamate release leading to the recruitment of NMDAr and plastic changes in the synaptic inhibition. Although: (1) the balance between excitation and inhibition is known to play a critical role in the spinal network; and (2) plastic changes in spinal excitation and inhibition have been studied separately, the relationship between these two mechanisms has not been investigated in detail. In the present work, we addressed the role of NMDA receptors in the modulation of GABAergic synaptic transmission in the DH network. Using tight-seal whole-cell recordings on adult mice DH neurons, we characterized the effect of NMDAr activation on inhibitory synaptic transmission and more especially on the GABAergic one. Our results show that, in a subset of neurons recorded in lamina II, NMDAr activation facilitates spontaneous and miniature GABAergic synaptic transmission with a target specificity on GABAergic interneurons. In contrast, NMDA reduced the mean amplitude of evoked GABAergic IPSCs. These results show that NMDAr modulate GABAergic transmission by a presynaptic mechanism of action. Using a pharmacological approach, we investigated the composition of NMDAr involved in this modulation of GABAergic synaptic transmission. We found that the NMDA-induced facilitation was mediated by the activation of NMDAr containing GluN2C/D subunits. Altogether, our results bring new insights on nociceptive information processing in the spinal cord network and plastic changes in synaptic inhibition that could underlie the development and maintenance of chronic pain. |
| first_indexed | 2024-12-12T11:43:10Z |
| format | Article |
| id | doaj.art-108487c54d1643e58495c2a6a57c4e6d |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-12T11:43:10Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-108487c54d1643e58495c2a6a57c4e6d2022-12-22T00:25:29ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-07-011510.3389/fnmol.2022.903087903087Modulation of GABAergic Synaptic Transmission by NMDA Receptors in the Dorsal Horn of the Spinal CordBenjamin Leonardon0Benjamin Leonardon1Lou Cathenaut2Lou Cathenaut3Louise Vial-Markiewicz4Louise Vial-Markiewicz5Sylvain Hugel6Rémy Schlichter7Rémy Schlichter8Perrine Inquimbert9Perrine Inquimbert10Centre National de la Recherche Scientifique, UPR 3212 Institute of Cellular and Integrative Neurosciences, Strasbourg, FranceUniversité de Strasbourg, Strasbourg, FranceCentre National de la Recherche Scientifique, UPR 3212 Institute of Cellular and Integrative Neurosciences, Strasbourg, FranceUniversité de Strasbourg, Strasbourg, FranceCentre National de la Recherche Scientifique, UPR 3212 Institute of Cellular and Integrative Neurosciences, Strasbourg, FranceUniversité de Strasbourg, Strasbourg, FranceCentre National de la Recherche Scientifique, UPR 3212 Institute of Cellular and Integrative Neurosciences, Strasbourg, FranceCentre National de la Recherche Scientifique, UPR 3212 Institute of Cellular and Integrative Neurosciences, Strasbourg, FranceUniversité de Strasbourg, Strasbourg, FranceCentre National de la Recherche Scientifique, UPR 3212 Institute of Cellular and Integrative Neurosciences, Strasbourg, FranceUniversité de Strasbourg, Strasbourg, FranceThe dorsal horn (DH) of the spinal cord is an important structure involved in the integration of nociceptive messages. Plastic changes in the properties of neuronal networks in the DH underlie the development of analgesia as well as of hyperalgesia and allodynia in acute and chronic pain states. Two key mechanisms are involved in these chronic pain states: increased electrical activities and glutamate release leading to the recruitment of NMDAr and plastic changes in the synaptic inhibition. Although: (1) the balance between excitation and inhibition is known to play a critical role in the spinal network; and (2) plastic changes in spinal excitation and inhibition have been studied separately, the relationship between these two mechanisms has not been investigated in detail. In the present work, we addressed the role of NMDA receptors in the modulation of GABAergic synaptic transmission in the DH network. Using tight-seal whole-cell recordings on adult mice DH neurons, we characterized the effect of NMDAr activation on inhibitory synaptic transmission and more especially on the GABAergic one. Our results show that, in a subset of neurons recorded in lamina II, NMDAr activation facilitates spontaneous and miniature GABAergic synaptic transmission with a target specificity on GABAergic interneurons. In contrast, NMDA reduced the mean amplitude of evoked GABAergic IPSCs. These results show that NMDAr modulate GABAergic transmission by a presynaptic mechanism of action. Using a pharmacological approach, we investigated the composition of NMDAr involved in this modulation of GABAergic synaptic transmission. We found that the NMDA-induced facilitation was mediated by the activation of NMDAr containing GluN2C/D subunits. Altogether, our results bring new insights on nociceptive information processing in the spinal cord network and plastic changes in synaptic inhibition that could underlie the development and maintenance of chronic pain.https://www.frontiersin.org/articles/10.3389/fnmol.2022.903087/fulldorsal hornsynaptic inhibitionNMDA receptorsnociceptionpain |
| spellingShingle | Benjamin Leonardon Benjamin Leonardon Lou Cathenaut Lou Cathenaut Louise Vial-Markiewicz Louise Vial-Markiewicz Sylvain Hugel Rémy Schlichter Rémy Schlichter Perrine Inquimbert Perrine Inquimbert Modulation of GABAergic Synaptic Transmission by NMDA Receptors in the Dorsal Horn of the Spinal Cord Frontiers in Molecular Neuroscience dorsal horn synaptic inhibition NMDA receptors nociception pain |
| title | Modulation of GABAergic Synaptic Transmission by NMDA Receptors in the Dorsal Horn of the Spinal Cord |
| title_full | Modulation of GABAergic Synaptic Transmission by NMDA Receptors in the Dorsal Horn of the Spinal Cord |
| title_fullStr | Modulation of GABAergic Synaptic Transmission by NMDA Receptors in the Dorsal Horn of the Spinal Cord |
| title_full_unstemmed | Modulation of GABAergic Synaptic Transmission by NMDA Receptors in the Dorsal Horn of the Spinal Cord |
| title_short | Modulation of GABAergic Synaptic Transmission by NMDA Receptors in the Dorsal Horn of the Spinal Cord |
| title_sort | modulation of gabaergic synaptic transmission by nmda receptors in the dorsal horn of the spinal cord |
| topic | dorsal horn synaptic inhibition NMDA receptors nociception pain |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.903087/full |
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