{"doi":"10.1101/2025.06.09.658722","title":"Microglia surveillance is directed toward neuron activation during sustained intracortical microstimulation","abstract":"Intracortical microstimulation (ICMS) is a widely used tool for neuroprostheses, but its long-term efficacy is often limited by biofouling and neuroinflammatory responses at the electrode-tissue interface. Microglia orchestrate neuroinflammation and regulate synaptic plasticity, and low-frequency stimulation has been shown to promote anti-inflammatory microglial phenotypes. We therefore examined, over the first three days post-implantation, how 10-Hz ICMS influences microglial-neuronal interactions in vivo using two-photon imaging in Cx3cr1-GFP/jRGECO1a mice. A one-hour session of 10-Hz ICMS did not induce overt morphological activation of microglia but increased their process motility, directing extensions toward both the electrode and neurons exhibiting elevated calcium activity. By post-implantation Day 2, microglial extensions were significantly biased toward neurons whose ΔF/F surpassed a 3 standard deviation threshold after stimulation onset (74.26° ± 11.83°) but shifted away from those same neurons after 40 min of continuous stimulation (116.99° ± 9.19°) (p = 0.001732), suggesting a dynamic, homeostatic response to sustained neuronal calcium elevations. Although multi-day electrode insertion accelerated microglial motility and polarization toward the device, 10-Hz ICMS alone did not alter microglial branching or soma shape. Microglial contact frequency scaled with neuronal adaptation profiles: depressed neurons received the most contacts immediately post-implant (1.15 ± 0.3 contacts; p = .0460). These findings reveal stimulus-associated, neuron-dependent surveillance behaviors of microglia during early post-implantation ICMS and implicate them as active participants in short-term modulation of cortical circuits.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":558241,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1458686,"name":"Knut Stieger","orcid":"0000-0002-8298-5629","position":1,"is_corresponding":false},{"id":1458687,"name":"Ke Chen","orcid":"0000-0001-9457-9364","position":2,"is_corresponding":false},{"id":362235,"name":"Guodong Zhang","orcid":"0000-0002-4310-6097","position":3,"is_corresponding":false},{"id":328509,"name":"Takashi D.Y. Kozai","orcid":"0000-0002-2507-3295","position":4,"is_corresponding":false},{"id":1459138,"name":"C Preszler","orcid":null,"position":0,"is_corresponding":true}],"reference_count":128,"raw_metadata":null,"created_at":"2026-07-19T02:55:25.969263Z","pmid":"40661573","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}