Astrocyte-induced firing in primary afferent axons

Summary: The large-caliber primary afferents innervating the spindles of the jaw-closing muscles have their cell bodies located centrally in the mesencephalic trigeminal nucleus (NVmes). We have shown, in an acid-induced jaw muscle chronic myalgia model, that these afferents exhibit increased excita...

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Main Authors: Fanny Gaudel, Julia Giraud, Philippe Morquette, Marc Couillard-Larocque, Dorly Verdier, Arlette Kolta
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225002664
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author Fanny Gaudel
Julia Giraud
Philippe Morquette
Marc Couillard-Larocque
Dorly Verdier
Arlette Kolta
author_facet Fanny Gaudel
Julia Giraud
Philippe Morquette
Marc Couillard-Larocque
Dorly Verdier
Arlette Kolta
author_sort Fanny Gaudel
collection DOAJ
description Summary: The large-caliber primary afferents innervating the spindles of the jaw-closing muscles have their cell bodies located centrally in the mesencephalic trigeminal nucleus (NVmes). We have shown, in an acid-induced jaw muscle chronic myalgia model, that these afferents exhibit increased excitability and ectopic discharges that emerge from subthreshold membrane oscillations (SMOs) supported by a persistent sodium current (INaP) exquisitely sensitive to extracellular Ca2+-decreases. Here, we explore if the Ca2+-binding astrocytic protein, S100β, contributes to this hyperexcitability emergence and aim to localize the site where ectopic discharge arises using whole-cell patch-clamp recordings on mice brain slices. We found that astrocytes, by lowering [Ca2+]e at focal points along the axons of NVmes neurons through S100β, enhance the amplitude of the NaV1.6-dependent SMOs, leading to ectopic firing. These findings suggest a crucial role for astrocytes in excitability regulation and raise questions about this neuron-astrocyte interaction as a key contributor to hyperexcitability in several pathologies.
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spelling doaj-art-ed42f45c26cf449580d2b86d8e6b8fcf2025-08-20T02:11:05ZengElsevieriScience2589-00422025-03-0128311200610.1016/j.isci.2025.112006Astrocyte-induced firing in primary afferent axonsFanny Gaudel0Julia Giraud1Philippe Morquette2Marc Couillard-Larocque3Dorly Verdier4Arlette Kolta5Département de Neurosciences, Université de Montréal, Montréal, QC, Canada; Centre Interdisciplinaire de Recherche sur le Cerveau et l’Apprentissage, Université de Montréal, Montréal, QC, CanadaDépartement de Neurosciences, Université de Montréal, Montréal, QC, CanadaDépartement de Neurosciences, Université de Montréal, Montréal, QC, Canada; F. M. Kirby Neurobiology Center and Department of Neurology, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USADépartement de Neurosciences, Université de Montréal, Montréal, QC, CanadaDépartement de Neurosciences, Université de Montréal, Montréal, QC, Canada; Centre Interdisciplinaire de Recherche sur le Cerveau et l’Apprentissage, Université de Montréal, Montréal, QC, CanadaDépartement de Neurosciences, Université de Montréal, Montréal, QC, Canada; Centre Interdisciplinaire de Recherche sur le Cerveau et l’Apprentissage, Université de Montréal, Montréal, QC, Canada; Faculté de Médecine Dentaire, Université de Montréal, Montréal, QC, Canada; Corresponding authorSummary: The large-caliber primary afferents innervating the spindles of the jaw-closing muscles have their cell bodies located centrally in the mesencephalic trigeminal nucleus (NVmes). We have shown, in an acid-induced jaw muscle chronic myalgia model, that these afferents exhibit increased excitability and ectopic discharges that emerge from subthreshold membrane oscillations (SMOs) supported by a persistent sodium current (INaP) exquisitely sensitive to extracellular Ca2+-decreases. Here, we explore if the Ca2+-binding astrocytic protein, S100β, contributes to this hyperexcitability emergence and aim to localize the site where ectopic discharge arises using whole-cell patch-clamp recordings on mice brain slices. We found that astrocytes, by lowering [Ca2+]e at focal points along the axons of NVmes neurons through S100β, enhance the amplitude of the NaV1.6-dependent SMOs, leading to ectopic firing. These findings suggest a crucial role for astrocytes in excitability regulation and raise questions about this neuron-astrocyte interaction as a key contributor to hyperexcitability in several pathologies.http://www.sciencedirect.com/science/article/pii/S2589004225002664neurosciencecell biology
spellingShingle Fanny Gaudel
Julia Giraud
Philippe Morquette
Marc Couillard-Larocque
Dorly Verdier
Arlette Kolta
Astrocyte-induced firing in primary afferent axons
iScience
neuroscience
cell biology
title Astrocyte-induced firing in primary afferent axons
title_full Astrocyte-induced firing in primary afferent axons
title_fullStr Astrocyte-induced firing in primary afferent axons
title_full_unstemmed Astrocyte-induced firing in primary afferent axons
title_short Astrocyte-induced firing in primary afferent axons
title_sort astrocyte induced firing in primary afferent axons
topic neuroscience
cell biology
url http://www.sciencedirect.com/science/article/pii/S2589004225002664
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AT juliagiraud astrocyteinducedfiringinprimaryafferentaxons
AT philippemorquette astrocyteinducedfiringinprimaryafferentaxons
AT marccouillardlarocque astrocyteinducedfiringinprimaryafferentaxons
AT dorlyverdier astrocyteinducedfiringinprimaryafferentaxons
AT arlettekolta astrocyteinducedfiringinprimaryafferentaxons