Astrocyte-induced firing in primary afferent axons

iScience, Journal Year: 2025, Volume and Issue: 28(3), P. 112006 - 112006

Published: Feb. 12, 2025

The large-caliber primary afferents innervating the spindles of jaw-closing muscles have their cell bodies located centrally in mesencephalic trigeminal nucleus (NVmes). We shown, an acid-induced jaw muscle chronic myalgia model, that these exhibit increased excitability and ectopic discharges emerge from subthreshold membrane oscillations (SMOs) supported by a persistent sodium current (I NaP) exquisitely sensitive to extracellular Ca2+-decreases. Here, we explore if Ca2+-binding astrocytic protein, S100β, contributes this hyperexcitability emergence aim localize site where discharge arises using whole-cell patch-clamp recordings on mice brain slices. found astrocytes, lowering [Ca2+]e at focal points along axons NVmes neurons through enhance amplitude NaV1.6-dependent SMOs, leading firing. These findings suggest crucial role for astrocytes regulation raise questions about neuron-astrocyte interaction as key contributor several pathologies.

Language: Английский

Prenatal sodium channel dysfunction in Dravet syndrome alters cortical development

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: May 9, 2025

Neurodevelopmental disorders associated with epilepsy are typically linked to postnatal dysfunction of synaptic proteins and ion channels, yet increasing evidence suggests a role for these before birth. The voltage-gated sodium channel Nav1.1, encoded by SCN1A, is well studied postnatally. SCN1A mutations result in broad range neurological phenotypes including developmental epileptic encephalopathies (DEEs Dravet syndrome, DS) fetal lethality. Here, we investigated the early corticogenesis. By integrating data from DS patient-derived forebrain models, mouse model, post-mortem tissue, report altered G2/M cell cycle transition, shift towards earlier neurogenic fate commitment. These changes lead cortical specification at birth throughout life. roles Nav1.1 complement well-known neuronal excitability. discoveries reveal new insights into pathogenesis non-canonical

Language: Английский

Activity-dependent development of the body’s touch receptors

Neuron, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

We report a role for activity in the development of primary sensory neurons that detect touch. Genetic deletion Piezo2, principal mechanosensitive ion channel somatosensory neurons, caused profound changes formation mechanosensory end-organ structures. Peripheral-nervous-system-specific voltage-gated sodium Nav1.6 (Scn8a), which resulted altered electrophysiological responses to mechanical stimuli, also disrupted neuron morphologies, supporting neuronal formation. Single-cell RNA sequencing Piezo2 mutants revealed gene expression activated by light forces, whereas other classes were minimally affected, and genetic Piezo2-dependent genes partially reproduced defects structures observed mutants. These findings indicate mechanically evoked acts early life shape maturation end-organs underlie our sense gentle

Language: Английский