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This study explored the relationship between microglial morphology and sleep\u2013wake cycles in mice. Using Iba1 immunostaining to identify microglia, we quantified morphological changes in microglia at different timepoints in multiple brain regions (cortex, hippocampus, basal forebrain, hindbrain, and cerebellum) in B6 male mice using semi\u2010automated 3D structural analysis. Simultaneously, in a separate group, we monitored wake and sleep stage\u2010specific brain activity using EEG\/EMG recordings. During natural sleep\u2013wake cycles, we observed increased microglial complexity (enlarged volume, territorial coverage, and ramification) during wakefulness, characterized by high\u2010frequency theta (8\u201312\u2009Hz) and gamma activity (30\u201380\u2009Hz). Conversely, during NREM sleep, which is dominated by delta activity (0.5\u20134\u2009Hz), microglia displayed reduced complexity. Notably, this pattern was absent in brain regions lacking direct functional connections to areas generating vigilance stage\u2010dependent thalamocortical oscillations. We then extended wakefulness to decouple circadian influence from sleep\u2013wake\u2010specific neuronal activity. This procedure attenuated the decrease in microglial complexity observed during natural sleep, suggesting a crucial role for neuronal activity. Subsequent recovery sleep restored microglial features, independent of the time of day (zeitgeber time). These findings reveal a dynamic interplay between vigilance stage\u2010specific thalamocortical activity and microglial morphology across various brain regions. This suggests a potential role for microglia in sleep regulation and warrants further investigation to understand the underlying mechanisms.<\/jats:p>","DOI":"10.1002\/glia.24617","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T06:24:14Z","timestamp":1726813454000},"page":"2344-2356","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Microglial morphology aligns with vigilance stage\u2010specific neuronal oscillations in a brain region\u2010dependent manner"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1047-064X","authenticated-orcid":false,"given":"Sarah","family":"Steffens","sequence":"first","affiliation":[{"name":"SLEEPWELL Research Program I Faculty of Medicine University of Helsinki  Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5693-0767","authenticated-orcid":false,"given":"Hilla","family":"M\u00e4kinen","sequence":"additional","affiliation":[{"name":"SLEEPWELL Research Program I Faculty of Medicine University of Helsinki  Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1843-7625","authenticated-orcid":false,"given":"Tarja","family":"Stenberg","sequence":"additional","affiliation":[{"name":"SLEEPWELL Research Program I Faculty of Medicine University of Helsinki  Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1725-574X","authenticated-orcid":false,"given":"Henna\u2010Kaisa","family":"Wigren","sequence":"additional","affiliation":[{"name":"SLEEPWELL Research Program I Faculty of Medicine University of Helsinki  Finland"},{"name":"Molecular and Integrative Biosciences Research Programme I Faculty of Biological and Environmental Sciences University of Helsinki  Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(93)90016-5"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-019-0223-4"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/ANNUREV-NEURO-091819-094557"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/BRV.12797"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0192-3"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(03)00055-8"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000014655"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3981-16.2017"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17062-2"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ctn8010005"},{"key":"e_1_2_11_12_1","first-page":"195","article-title":"A two process model of sleep regulation","volume":"1","author":"Borb\u00e9ly A. 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