A class-specific effect of dysmyelination on the excitability of hippocampal interneurons
The role of myelination for axonal conduction is well-established in projection neurons but little is known about its significance in GABAergic interneurons. Myelination is discontinuous along interneuron axons and the mechanisms controlling myelin patterning and segregation of ion channels at the n...
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eLife Sciences Publications Ltd
2023-10-01
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| Online Access: | https://elifesciences.org/articles/86469 |
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| author | Delphine Pinatel Edouard Pearlstein Giulia Bonetto Laurence Goutebroze Domna Karagogeos Valérie Crepel Catherine Faivre-Sarrailh |
| author_facet | Delphine Pinatel Edouard Pearlstein Giulia Bonetto Laurence Goutebroze Domna Karagogeos Valérie Crepel Catherine Faivre-Sarrailh |
| author_sort | Delphine Pinatel |
| collection | DOAJ |
| description | The role of myelination for axonal conduction is well-established in projection neurons but little is known about its significance in GABAergic interneurons. Myelination is discontinuous along interneuron axons and the mechanisms controlling myelin patterning and segregation of ion channels at the nodes of Ranvier have not been elucidated. Protein 4.1B is implicated in the organization of the nodes of Ranvier as a linker between paranodal and juxtaparanodal membrane proteins to the spectrin cytoskeleton. In the present study, 4.1B KO mice are used as a genetic model to analyze the functional role of myelin in Lhx6-positive parvalbumin (PV) and somatostatin (SST) neurons, two major classes of GABAergic neurons in the hippocampus. We show that 4.1B-deficiency induces disruption of juxtaparanodal K+ channel clustering and mislocalization of nodal or heminodal Na+ channels. Strikingly, 4.1B-deficiency causes loss of myelin in GABAergic axons in the hippocampus. In particular, stratum oriens SST cells display severe axonal dysmyelination and a reduced excitability. This reduced excitability is associated with a decrease in occurrence probability of small amplitude synaptic inhibitory events on pyramidal cells. In contrast, stratum pyramidale fast-spiking PV cells do not appear affected. In conclusion, our results indicate a class-specific effect of dysmyelination on the excitability of hippocampal interneurons associated with a functional alteration of inhibitory drive. |
| first_indexed | 2024-03-11T14:28:33Z |
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| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-11T14:28:33Z |
| publishDate | 2023-10-01 |
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| series | eLife |
| spelling | doaj.art-c57bdf291b3745bc866743ea100882872023-10-31T12:23:13ZengeLife Sciences Publications LtdeLife2050-084X2023-10-011210.7554/eLife.86469A class-specific effect of dysmyelination on the excitability of hippocampal interneuronsDelphine Pinatel0Edouard Pearlstein1https://orcid.org/0000-0001-9405-5667Giulia Bonetto2https://orcid.org/0000-0003-1469-2004Laurence Goutebroze3Domna Karagogeos4Valérie Crepel5https://orcid.org/0000-0003-0408-3766Catherine Faivre-Sarrailh6https://orcid.org/0000-0002-1718-0533INMED, INSERM, Aix Marseille Université, Marseille, FranceINMED, INSERM, Aix Marseille Université, Marseille, FranceINMED, INSERM, Aix Marseille Université, Marseille, FranceINSERM, Institut du Fer à Moulin, Sorbonne Université, Faculté des Sciences et Ingénierie, Paris, FranceDepartment of Basic Sciences, University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, University of Crete, Heraklion, GreeceINMED, INSERM, Aix Marseille Université, Marseille, FranceINMED, INSERM, Aix Marseille Université, Marseille, FranceThe role of myelination for axonal conduction is well-established in projection neurons but little is known about its significance in GABAergic interneurons. Myelination is discontinuous along interneuron axons and the mechanisms controlling myelin patterning and segregation of ion channels at the nodes of Ranvier have not been elucidated. Protein 4.1B is implicated in the organization of the nodes of Ranvier as a linker between paranodal and juxtaparanodal membrane proteins to the spectrin cytoskeleton. In the present study, 4.1B KO mice are used as a genetic model to analyze the functional role of myelin in Lhx6-positive parvalbumin (PV) and somatostatin (SST) neurons, two major classes of GABAergic neurons in the hippocampus. We show that 4.1B-deficiency induces disruption of juxtaparanodal K+ channel clustering and mislocalization of nodal or heminodal Na+ channels. Strikingly, 4.1B-deficiency causes loss of myelin in GABAergic axons in the hippocampus. In particular, stratum oriens SST cells display severe axonal dysmyelination and a reduced excitability. This reduced excitability is associated with a decrease in occurrence probability of small amplitude synaptic inhibitory events on pyramidal cells. In contrast, stratum pyramidale fast-spiking PV cells do not appear affected. In conclusion, our results indicate a class-specific effect of dysmyelination on the excitability of hippocampal interneurons associated with a functional alteration of inhibitory drive.https://elifesciences.org/articles/86469myelinhippocampusGABAergic interneurons |
| spellingShingle | Delphine Pinatel Edouard Pearlstein Giulia Bonetto Laurence Goutebroze Domna Karagogeos Valérie Crepel Catherine Faivre-Sarrailh A class-specific effect of dysmyelination on the excitability of hippocampal interneurons eLife myelin hippocampus GABAergic interneurons |
| title | A class-specific effect of dysmyelination on the excitability of hippocampal interneurons |
| title_full | A class-specific effect of dysmyelination on the excitability of hippocampal interneurons |
| title_fullStr | A class-specific effect of dysmyelination on the excitability of hippocampal interneurons |
| title_full_unstemmed | A class-specific effect of dysmyelination on the excitability of hippocampal interneurons |
| title_short | A class-specific effect of dysmyelination on the excitability of hippocampal interneurons |
| title_sort | class specific effect of dysmyelination on the excitability of hippocampal interneurons |
| topic | myelin hippocampus GABAergic interneurons |
| url | https://elifesciences.org/articles/86469 |
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