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Autonomic imbalance (sympathetic overactivity and parasympathetic withdrawal) has emerged as a causal contributor of CIH\u2010induced cardiovascular disease. Previously, we showed that CIH remodels the parasympathetic pathway. However, whether CIH induces remodelling of the cardiac sympathetic innervation remains unknown. Mice (male, C57BL\/6J, 2\u20133\u00a0months) were exposed to either room air (RA, 21% O<jats:sub>2<\/jats:sub>) or CIH (alternating 21% and 5.7% O<jats:sub>2<\/jats:sub>, every 6\u00a0min, 10 h\u00a0day<jats:sup>\u20131<\/jats:sup>) for 8\u201310\u00a0weeks. Flat\u2010mounts of their left and right atria were immunohistochemically labelled for tyrosine hydroxylase (TH, a sympathetic marker). Using a confocal microscope (or fluorescence microscope) and Neurlocudia 360\u00a0digitization and tracing system, we scanned both the left and right atria and quantitatively analysed the sympathetic axon density in both groups. The segmentation data was mapped onto a 3D mouse heart scaffold. Our findings indicated that CIH significantly remodelled the TH immunoreactive (\u2010IR) innervation of the atria by increasing its density at the sinoatrial node, the auricles and the major veins attached to the atria (<jats:italic>P<\/jats:italic> &lt; 0.05, <jats:italic>n<\/jats:italic>\u00a0=\u00a07). Additionally, CIH increased the branching points of TH\u2010IR axons and decreased the distance between varicosities. Abnormal patterns of TH\u2010IR axons around intrinsic cardiac ganglia were also found following CIH. We postulate that the increased sympathetic innervation may further amplify the effects of enhanced CIH\u2010induced central sympathetic drive to the heart. Our work provides an anatomical foundation for the understanding of CIH\u2010induced autonomic imbalance.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15786-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Chronic intermittent hypoxia (CIH, a model for sleep apnoea) causes sympathetic overactivity, cardiovascular remodelling and hypertension.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We determined the effect of CIH on sympathetic innervation of the mouse atria.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:italic>In vivo<\/jats:italic> CIH for 8\u201310\u00a0weeks resulted in an aberrant axonal pattern around the principal neurons within intrinsic cardiac ganglia and an increase in the density, branching point, tortuosity of catecholaminergic axons and atrial wall thickness.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Utilizing mapping tool available from NIH (SPARC) Program, the topographical distribution of the catecholaminergic innervation of the atria were integrated into a novel 3D heart scaffold for precise anatomical distribution and holistic quantitative comparison between normal and CIH mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This work provides a unique neuroanatomical understanding of the pathophysiology of CIH\u2010induced autonomic remodelling.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp284961","type":"journal-article","created":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T14:36:36Z","timestamp":1703860596000},"page":"49-71","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Chronic intermittent hypoxia remodels catecholaminergic nerve innervation in mouse atria"],"prefix":"10.1113","volume":"602","author":[{"given":"Ariege","family":"Bizanti","sequence":"first","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine University of Central Florida  Orlando FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine University of Central Florida  Orlando FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zulema","family":"Toledo","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine University of Central Florida  Orlando FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohlton T.","family":"Bendowski","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine University of Central Florida  Orlando FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0757-1979","authenticated-orcid":false,"given":"Scott W.","family":"Harden","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine University of Central Florida  Orlando FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anas","family":"Mistareehi","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine University of Central Florida  Orlando FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Chen","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine University of Central Florida  Orlando FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Gozal","sequence":"additional","affiliation":[{"name":"Joan C. 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