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For example, acute stress produces persisting decreases in voluntary physical activity as well as molecular changes in the striatum, a brain region that regulates voluntary physical activity and other motivated behaviors. Microglia, the primary immune cells of the central nervous system, are positioned at the interface between neural responses to stress and neural coordination of voluntary activity in that they respond to stress, sense molecular changes in the striatum, and modulate neuronal activity. However, the role of striatal microglia in stress\u2010induced long\u2010term suppression of voluntary activity is unknown. Here, we employ single\u2010nucleus RNA sequencing to investigate how stress and exercise impact the biology of microglia in the striatum. We find that striatal microglia display altered activation profiles 6\u2009weeks after an acute stressor. Furthermore, we show that access to a running wheel is associated with an additional and distinct microglial activation profile characterized by upregulation of genes related to complement components and phagocytosis pathways. Finally, we find that distinct gene sets show expression changes associated with general access to a running wheel versus variation in running levels. Taken together, our results deepen our understanding of the diverse molecular states that striatal microglia assume in response to stress and exercise and suggest that microglia exhibit a broader range of functional states than previously thought.<\/jats:p>","DOI":"10.1111\/gbb.70019","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:19:31Z","timestamp":1741738771000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Single\u2010Nucleus\n                    <scp>RNA<\/scp>\n                    Sequencing Reveals Enduring Signatures of Acute Stress and Chronic Exercise in Striatal Microglia"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0654-6330","authenticated-orcid":false,"given":"Meghan G.","family":"Connolly","sequence":"first","affiliation":[{"name":"Neuroscience Program University of Illinois Urbana\u2010Champaign  Urbana Illinois 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