Astrocyte-induced firing in primary afferent axons

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-02-12 DOI:10.1016/j.isci.2025.112006

Fanny Gaudel , Julia Giraud , Philippe Morquette , Marc Couillard-Larocque , Dorly Verdier , Arlette Kolta

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Abstract

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 (I_NaP) 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 Na_V1.6-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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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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