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Background <p>Chronically implanted electrodes offer a promising approach for treating neurological disorders <i>via</i> brain-computer interfaces, yet their long-term efficacy is compromised by the neuroinflammatory foreign body response. While neurons are central to both electrode function and inflammatory regulation, their specific responses post-implantation remain poorly characterized. Here, we combined single-nucleus RNA sequencing (snRNA-seq) and immunofluorescence to delineate the spatiotemporal dynamics of neuronal subtypes in the rat motor cortex at 3, 25, and 50 days after electrode implantation.</p> Results <p>We identified 22 distinct neuronal subpopulations, among which clusters 5, 6, and 8 emerged as injury-responsive subtypes during the acute phase (3 days), exhibiting a specific upregulation of <i>Tmsb4x</i>, a key regulator of neuronal plasticity and repair. Furthermore, our analysis revealed activated signaling pathways mediating neuron-glia communication, most notably the Ptn-Sdc4 and Il34/Csf1-Csf1R axes between neurons and astrocytes.</p> Conclusions <p>These findings provide a high-resolution map of neuronal adaptation to intracortical implants, uncovering previously unknown repair-associated neuronal subtypes and specific ligand-receptor pairs that coordinate the neuroinflammatory microenvironment, which offers novel insights and potential therapeutic targets for improving the biocompatibility and long-term stability of neural electrodes.</p> Graphical abstract <p></p>

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Spatiotemporal dynamics of neuronal subtypes and their interactions with glia following intracortical electrode implantation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月29日

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  • Zhi Zhao,
  • Xiaoge Duan,
  • Jiaqi Luo,
  • Zhaoyuan He,
  • Yuxue Zhang,
  • Meiting Wang,
  • Jiaoqin Qin,
  • Sen Lin,
  • Hailan Chen

摘要

Background

Chronically implanted electrodes offer a promising approach for treating neurological disorders via brain-computer interfaces, yet their long-term efficacy is compromised by the neuroinflammatory foreign body response. While neurons are central to both electrode function and inflammatory regulation, their specific responses post-implantation remain poorly characterized. Here, we combined single-nucleus RNA sequencing (snRNA-seq) and immunofluorescence to delineate the spatiotemporal dynamics of neuronal subtypes in the rat motor cortex at 3, 25, and 50 days after electrode implantation.

Results

We identified 22 distinct neuronal subpopulations, among which clusters 5, 6, and 8 emerged as injury-responsive subtypes during the acute phase (3 days), exhibiting a specific upregulation of Tmsb4x, a key regulator of neuronal plasticity and repair. Furthermore, our analysis revealed activated signaling pathways mediating neuron-glia communication, most notably the Ptn-Sdc4 and Il34/Csf1-Csf1R axes between neurons and astrocytes.

Conclusions

These findings provide a high-resolution map of neuronal adaptation to intracortical implants, uncovering previously unknown repair-associated neuronal subtypes and specific ligand-receptor pairs that coordinate the neuroinflammatory microenvironment, which offers novel insights and potential therapeutic targets for improving the biocompatibility and long-term stability of neural electrodes.

Graphical abstract