GABAergic neurons can facilitate the propagation of cortical spreading depolarization: experiments in mouse neocortical slices and a novel neural field computational model
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Le résumé fourni par la source
Cortical spreading depolarization (CSD) is a wave of depolarization with local onset and extended propagation implicated in several pathological conditions. Its mechanisms have been extensively investigated, including our recent studies showing with experimental and computational approaches that the hyperactivity of GABAergic neurons' can initiate migraine-related CSD because of spiking-generated extracellular potassium ([Formula: see text]) build-up. However, less is known about the role played by GABAergic neurons in CSD propagation. Here we studied mechanisms of CSD propagation, focusing on the role of GABAergic neurons, with experiments performed in mouse brain slices and with a new spatially extended neural field computational model. Experimentally, we induced CSD by applying brief puffs of potassium chloride (KCl) in somatosensory cortex slices from wild type and VGAT-ChR2-tdtomato mice, which specifically express the excitatory opsin channelrhodopsin (ChR2) in GABAergic neurons. We evaluated the role of GABAergic neurons in CSD propagation by modulating their activity with optogenetic illumination and their synaptic connections with pharmacological tools. We have developed the computational model to obtain realistic simulations of both initiation and propagation of CSD. It includes large populations of interconnected excitatory and inhibitory neurons, as well as the effect of extracellular ion concentrations on their features. We found that the decrease of the synaptic activity of GABAergic neurons can enhance CSD propagation, because of the reduction of the inhibitory synaptic weight, whereas their spiking activity can enhance CSD propagation because of extracellular [Formula: see text] upload. However, differently than for CSD initiation, the latter effect is normally hidden by the action of GABAergic synaptic transmission. A reduction of GABAergic synaptic transmission, which can be observed in pathological states, can reveal the potentiating effect of the [Formula: see text] upload induced by GABAergic activation. The neural field model that we implemented can generate accurate simulations of CSD, providing testable hypotheses on mechanisms, and can also be used for modeling other (patho)-physiological activities of neuronal networks.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- GABAergic neurons can facilitate the propagation of cortical spreading depolarization: experiments in mouse neocortical slices and a novel neural field computational model
- Date Crossref
- 04/06/2025
- Éditeur
- Public Library of Science (PLoS)
- 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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Institut national de recherche en sciences et technologies du numérique pays non établi dans la noticeOrganisme public
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Université de Montpellier pays non établi dans la noticeUniversité ou école supérieure
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MATHNEURO: Mathématiques pour les Neurosciences pays non établi dans la noticeStructure de recherche
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Centre National de la Recherche Scientifique pays non établi dans la noticeOrganisme public
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Inserm pays non établi dans la noticeOrganisme public
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Université Côte d'Azur pays non établi dans la noticeUniversité ou école supérieure
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Fondation Sophia Antipolis pays non établi dans la noticeInstitution
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Institut de Pharmacologie Moléculaire et Cellulaire pays non établi dans la noticeStructure de recherche
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Basque Center for Applied Mathematics pays non établi dans la noticeUniversité ou école supérieure
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Amsterdam Neuroscience pays non établi dans la noticeStructure de recherche
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Vrije Universiteit Amsterdam Department of Mathematics pays non établi dans la noticeUniversité ou école supérieure
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Inria Branch of the University of Montpellier MathNeuro Team pays non établi dans la noticeUniversité ou école supérieure
Institut national de recherche en sciences et technologies du numérique, Université de Montpellier et MATHNEURO: Mathématiques pour les Neurosciences, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.