Topographical mapping of catecholaminergic axon innervation in the flat-mounts of the mouse atria: a quantitative analysis
Abstract The sympathetic nervous system is crucial for controlling multiple cardiac functions. However, a comprehensive, detailed neuroanatomical map of the sympathetic innervation of the heart is unavailable. Here, we used a combination of state-of-the-art techniques, including flat-mount tissue pr...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-27727-9 |
| _version_ | 1797850133589655552 |
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| author | Yuanyuan Zhang Ariege Bizanti Scott W. Harden Jin Chen Kohlton Bendowski Donald B. Hoover David Gozal Kalyanam Shivkumar Maci Heal Susan Tappan Zixi Jack Cheng |
| author_facet | Yuanyuan Zhang Ariege Bizanti Scott W. Harden Jin Chen Kohlton Bendowski Donald B. Hoover David Gozal Kalyanam Shivkumar Maci Heal Susan Tappan Zixi Jack Cheng |
| author_sort | Yuanyuan Zhang |
| collection | DOAJ |
| description | Abstract The sympathetic nervous system is crucial for controlling multiple cardiac functions. However, a comprehensive, detailed neuroanatomical map of the sympathetic innervation of the heart is unavailable. Here, we used a combination of state-of-the-art techniques, including flat-mount tissue processing, immunohistochemistry for tyrosine hydroxylase (TH, a sympathetic marker), confocal microscopy and Neurolucida 360 software to trace, digitize, and quantitatively map the topographical distribution of the sympathetic postganglionic innervation in whole atria of C57Bl/6 J mice. We found that (1) 4–5 major extrinsic TH-IR nerve bundles entered the atria at the superior vena cava, right atrium (RA), left precaval vein and the root of the pulmonary veins (PVs) in the left atrium (LA). Although these bundles projected to different areas of the atria, their projection fields partially overlapped. (2) TH-IR axon and terminal density varied considerably between different sites of the atria with the greatest density of innervation near the sinoatrial node region (P < 0.05, n = 6). (3) TH-IR axons also innervated blood vessels and adipocytes. (4) Many principal neurons in intrinsic cardiac ganglia and small intensely fluorescent cells were also strongly TH-IR. Our work provides a comprehensive topographical map of the catecholaminergic efferent axon morphology, innervation, and distribution in the whole atria at single cell/axon/varicosity scale that may be used in future studies to create a cardiac sympathetic-brain atlas. |
| first_indexed | 2024-04-09T18:55:26Z |
| format | Article |
| id | doaj.art-e340f3bc4a02456abe92439c9d8f290f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T18:55:26Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e340f3bc4a02456abe92439c9d8f290f2023-04-09T11:13:46ZengNature PortfolioScientific Reports2045-23222023-04-0113112110.1038/s41598-023-27727-9Topographical mapping of catecholaminergic axon innervation in the flat-mounts of the mouse atria: a quantitative analysisYuanyuan Zhang0Ariege Bizanti1Scott W. Harden2Jin Chen3Kohlton Bendowski4Donald B. Hoover5David Gozal6Kalyanam Shivkumar7Maci Heal8Susan Tappan9Zixi Jack Cheng10Burnett School of Biomedical Sciences, College of Medicine, University of Central FloridaBurnett School of Biomedical Sciences, College of Medicine, University of Central FloridaBurnett School of Biomedical Sciences, College of Medicine, University of Central FloridaBurnett School of Biomedical Sciences, College of Medicine, University of Central FloridaBurnett School of Biomedical Sciences, College of Medicine, University of Central FloridaDepartment of Biomedical Sciences, Quillen College of Medicine, East Tennessee State UniversityDepartment of Child Health and Child Health Research Institute, University of Missouri School of MedicineDepartment of Medicine, Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, University of CaliforniaMBF BioscienceRock Maple ScienceBurnett School of Biomedical Sciences, College of Medicine, University of Central FloridaAbstract The sympathetic nervous system is crucial for controlling multiple cardiac functions. However, a comprehensive, detailed neuroanatomical map of the sympathetic innervation of the heart is unavailable. Here, we used a combination of state-of-the-art techniques, including flat-mount tissue processing, immunohistochemistry for tyrosine hydroxylase (TH, a sympathetic marker), confocal microscopy and Neurolucida 360 software to trace, digitize, and quantitatively map the topographical distribution of the sympathetic postganglionic innervation in whole atria of C57Bl/6 J mice. We found that (1) 4–5 major extrinsic TH-IR nerve bundles entered the atria at the superior vena cava, right atrium (RA), left precaval vein and the root of the pulmonary veins (PVs) in the left atrium (LA). Although these bundles projected to different areas of the atria, their projection fields partially overlapped. (2) TH-IR axon and terminal density varied considerably between different sites of the atria with the greatest density of innervation near the sinoatrial node region (P < 0.05, n = 6). (3) TH-IR axons also innervated blood vessels and adipocytes. (4) Many principal neurons in intrinsic cardiac ganglia and small intensely fluorescent cells were also strongly TH-IR. Our work provides a comprehensive topographical map of the catecholaminergic efferent axon morphology, innervation, and distribution in the whole atria at single cell/axon/varicosity scale that may be used in future studies to create a cardiac sympathetic-brain atlas.https://doi.org/10.1038/s41598-023-27727-9 |
| spellingShingle | Yuanyuan Zhang Ariege Bizanti Scott W. Harden Jin Chen Kohlton Bendowski Donald B. Hoover David Gozal Kalyanam Shivkumar Maci Heal Susan Tappan Zixi Jack Cheng Topographical mapping of catecholaminergic axon innervation in the flat-mounts of the mouse atria: a quantitative analysis Scientific Reports |
| title | Topographical mapping of catecholaminergic axon innervation in the flat-mounts of the mouse atria: a quantitative analysis |
| title_full | Topographical mapping of catecholaminergic axon innervation in the flat-mounts of the mouse atria: a quantitative analysis |
| title_fullStr | Topographical mapping of catecholaminergic axon innervation in the flat-mounts of the mouse atria: a quantitative analysis |
| title_full_unstemmed | Topographical mapping of catecholaminergic axon innervation in the flat-mounts of the mouse atria: a quantitative analysis |
| title_short | Topographical mapping of catecholaminergic axon innervation in the flat-mounts of the mouse atria: a quantitative analysis |
| title_sort | topographical mapping of catecholaminergic axon innervation in the flat mounts of the mouse atria a quantitative analysis |
| url | https://doi.org/10.1038/s41598-023-27727-9 |
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