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...

Full description

Saved in:
Bibliographic Details
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
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225002664
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2589-0042