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Neural Eng."],"published-print":{"date-parts":[[2026,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Objective.<\/jats:italic>\n                    Intracortical microstimulation (ICMS) is a widely used tool for neuroprostheses, but its long-term efficacy is often limited by foreign body response 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.\n                    <jats:italic>Approach.<\/jats:italic>\n                    We investigated how 10 Hz ICMS influences microglia\u2013neuron interactions during the first three days post-implantation using\n                    <jats:italic>in vivo<\/jats:italic>\n                    two-photon imaging in Cx3cr1-GFP\/jRGECO1a mice. Microglial motility, morphology, and process orientation were tracked relative to electrode placement and neuronal calcium activity (measured as change in fluorescence, \u0394\n                    <jats:italic>F<\/jats:italic>\n                    \/\n                    <jats:italic>F<\/jats:italic>\n                    ).\n                    <jats:italic>Main results.<\/jats:italic>\n                    A 1 h session of 10 Hz ICMS did not induce overt classical morphological activation of microglia but robustly increased process motility, with extensions dynamically tracking neurons showing early activation or subsequent functional suppression. By post-implantation Day 2, microglial processes were significantly more likely to engage neurons with high early calcium responses after stimulation onset (mean orientation angle: 74.3\u00b0 \u00b1 11.8\u00b0), but this engagement shifted during prolonged stimulation (117.0\u00b0 \u00b1 9.2\u00b0,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.0017), indicating context-dependent interactions. Contact frequency scaled with neuronal adaptation profiles, and neurons exhibiting depressed activity received the most contacts immediately after implantation (1.2 \u00b1 0.3 contacts,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.046).\n                    <jats:italic>Significance.<\/jats:italic>\n                    These findings reveal stimulus-associated, neuron-dependent surveillance behaviors of microglia during early post-implantation ICMS and suggest that microglia actively participate in short-term modulation of stimulated cortical circuits.\n                  <\/jats:p>","DOI":"10.1088\/1741-2552\/ae4652","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T22:51:11Z","timestamp":1771282271000},"page":"016033","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Microglia surveillance is directed toward neuron activation during sustained intracortical microstimulation"],"prefix":"10.1088","volume":"23","author":[{"given":"Colin","family":"Preszler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin C","family":"Stieger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangfeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2507-3295","authenticated-orcid":true,"given":"Takashi D Y","family":"Kozai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"jneae4652bib1","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/s13578-023-01085-5","type":"journal-article","article-title":"Intensity-dependent gamma electrical stimulation regulates microglial activation, reduces beta-amyloid load, and facilitates memory in a mouse model of Alzheimer\u2019s disease","volume":"13","author":"Liu","year":"2023","journal-title":"Cell Biosci."},{"key":"jneae4652bib2","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/j.brs.2022.05.021","type":"journal-article","article-title":"Effects of stimulus pulse rate on somatosensory adaptation in the human cortex","volume":"15","author":"Hughes","year":"2022","journal-title":"Brain Stimul."},{"key":"jneae4652bib3","doi-asserted-by":"publisher","DOI":"10.1172\/JCI151331","type":"journal-article","article-title":"Visual percepts evoked with an intracortical 96-channel microelectrode array inserted in human occipital cortex","volume":"131","author":"Fern\u00e1ndez","year":"2021","journal-title":"J. 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