Parasympathetic and sympathetic axons are bundled in the cardiac ventricles and undergo physiological reinnervation during heart regeneration

• Published in: iScience Vol. 26; no. 10; p. 107709
• Main Authors: Salamon, Rebecca J., Halbe, Poorva, Kasberg, William, Bae, Jiyoung, Audhya, Anjon, Mahmoud, Ahmed I.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.10.2023; Elsevier
• Subjects: Cell biology; Molecular biology; Neuroscience; Cell biology; Molecular biology; Neuroscience
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.107709

Sympathetic innervation influences homeostasis, repair, and pathology in the cardiac ventricles; in contrast, parasympathetic innervation is considered to have minimal contribution and influence in the ventricles. Here, we use genetic models, whole-mount imaging, and three-dimensional modeling to define cardiac nerve architecture during development, disease, and regeneration. Our approach reveals that parasympathetic nerves extensively innervate the cardiac ventricles. Furthermore, we identify that parasympathetic and sympathetic axons develop synchronously and are bundled throughout the ventricles. We further investigate cardiac nerve remodeling in the regenerative neonatal and the non-regenerative postnatal mouse heart. Our results show that the regenerating myocardium undergoes a unique process of physiological reinnervation, where proper nerve distribution and architecture is reestablished, in stark contrast to the non-regenerating heart. Mechanistically, we demonstrate that physiological reinnervation during regeneration is dependent on collateral artery formation. Our results reveal clinically significant insights into cardiac nerve plasticity which can identify new therapies for cardiac disease. [Display omitted] •Parasympathetic and sympathetic nerves are bundled in the cardiac ventricles•Physiological reinnervation takes place during heart regeneration•Sympathetic and parasympathetic axons reinnervate the regenerating heart•Reinnervation during regeneration is dependent on collateral artery formation Molecular biology; Neuroscience; Cell biology