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However, neurons and glial cells' heterogeneity and intercellular signaling mechanisms following electrode implantation remain poorly resolved, which is responsible for direct dysfunction. Here, we applied single\u2010nucleus RNA sequencing (snRNA\u2010seq) to profile the peri\u2010implant microenvironment in rat motor cortex tissue at 3, 25, and 50\u2009days post\u2010electrode implantation. Integrated bioinformatic analyses, including clustering, pseudotemporal trajectory reconstruction, and cell\u2013cell communication inference, revealed a coordinated cellular response. We identified a pathologic microglial subpopulation (marked by Gpnmb, SPP1, and CD63) and a scar\u2010associated astrocytic subtype (characterized by Mctp1 and Lrrc7) that progressively dominate the peri\u2010implant niche. Crucially, we reveal that neurons orchestrate these processes via CX3CL1\u2010CX3CR1 signaling, modulating microglial polarization and PTN\u2010ALK\/Ptpprz1 interaction, promoting astrogliosis and scar formation. These findings define the dynamic neuron\u2013glia signaling landscape surrounding chronically implanted electrodes and provide mechanistic insight into how modulating cell\u2013cell communication may improve the long\u2010term biocompatibility of neural interfaces.<\/jats:p>","DOI":"10.1002\/glia.70148","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T04:11:11Z","timestamp":1773634271000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Single\u2010Nucleus Transcriptomics Reveals Microglial State Transitions and Astrocytic Trajectory Divergence During Glial Remodeling Induced by Intracortical Electrode Implantation"],"prefix":"10.1002","volume":"74","author":[{"given":"Zhi","family":"Zhao","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention Guangxi University  Nanning Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoge","family":"Duan","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention Guangxi University  Nanning Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanjun","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention Guangxi University  Nanning Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Medical School of Guangxi University Guangxi University  Nanning Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiting","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical School of Guangxi University 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