3D single cell scale anatomical map of sex-dependent variability of the rat intrinsic cardiac nervous system

Summary We developed and analyzed a single cell scale anatomical map of the rat intrinsic cardiac nervous system (ICNS) across four male and three female hearts. We find the ICNS has a reliable structural organizational plan across individuals that provide the foundation for further analyses of the ICNS in cardiac function and disease. The distribution of the ICNS was evaluated by 3D visualization and data-driven clustering. The pattern, distribution, and clustering of ICNS neurons across all male and female rat hearts is highly conserved, demonstrating a coherent organizational plan where distinct clusters of neurons are consistently localized. Female hearts had fewer neurons, lower packing density, and slightly reduced distribution, but with identical localization. We registered the anatomical data from each heart to a geometric scaffold, normalizing their 3D coordinates for standardization of common anatomical planes and providing a path where multiple experimental results and data types can be integrated and compared.
Graphical abstract
Highlights • 3D anatomical map of rat intrinsic cardiac nervous system • Preferential organization of neurons in select cardiac anatomical regions • Conserved anatomical organization of intrinsic cardiac neurons across sexes • Generalized 3D scaffold for mapping of high-resolution cardiac anatomical data
Biology of gender; Cardiovascular medicine; Imaging anatomy; Systems neuroscience