A class-specific effect of dysmyelination on the excitability of hippocampal interneurons
- INSERM, Aix Marseille University, France
- INSERM UMR-S 1270, Sorbonne Universite, France
- University of Crete, Greece
Abstract
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.
Data availability
All data generated or analyzed during this study are included in the manuscript (source data files for Figure 1-9)
Article and author information
Author details
Edouard Pearlstein
Catherine Faivre-Sarrailh
Funding
Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques (Postdoc fellowship)
- Delphine Pinatel
Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques (Grant)
- Domna Karagogeos
Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques (Grant)
- Catherine Faivre-Sarrailh
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Katalin Toth, University of Ottawa, Canada
Ethics
Animal experimentation: The care and use of mice in all experiments were carried out according to the European and Institutional guidelines for the care and use of laboratory animals and approved by the local authority (laboratory's agreement number D13-055-8, Préfecture des Bouches du Rhône).
Version history
- Preprint posted: January 10, 2023 (view preprint)
- Received: January 27, 2023
- Accepted: October 13, 2023
- Accepted Manuscript published: October 16, 2023 (version 1)
- Version of Record published: October 31, 2023 (version 2)
Copyright
© 2023, Pinatel et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A class-specific effect of dysmyelination on the excitability of hippocampal interneurons
eLife 12:e86469.
https://doi.org/10.7554/eLife.86469
Further reading
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Evidence suggests that subcortical structures play a role in high-level cognitive functions such as the allocation of spatial attention. While there is abundant evidence in humans for posterior alpha band oscillations being modulated by spatial attention, little is known about how subcortical regions contribute to these oscillatory modulations, particularly under varying conditions of cognitive challenge. In this study, we combined MEG and structural MRI data to investigate the role of subcortical structures in controlling the allocation of attentional resources by employing a cued spatial attention paradigm with varying levels of perceptual load. We asked whether hemispheric lateralization of volumetric measures of the thalamus and basal ganglia predicted the hemispheric modulation of alpha-band power. Lateral asymmetry of the globus pallidus, caudate nucleus, and thalamus predicted attention-related modulations of posterior alpha oscillations. When the perceptual load was applied to the target and the distractor was salient caudate nucleus asymmetry predicted alpha-band modulations. Globus pallidus was predictive of alpha-band modulations when either the target had a high load, or the distractor was salient, but not both. Finally, the asymmetry of the thalamus predicted alpha band modulation when neither component of the task was perceptually demanding. In addition to delivering new insight into the subcortical circuity controlling alpha oscillations with spatial attention, our finding might also have clinical applications. We provide a framework that could be followed for detecting how structural changes in subcortical regions that are associated with neurological disorders can be reflected in the modulation of oscillatory brain activity.
