A Comprehensive Integrated Anatomical And Molecular Atlas Of Rodent Intrinsic Cardiac Nervous System

Abstract

In this study, we developed, coordinated, and integrated several technologies including novel whole organ imaging, software development to support the very first precise 3D neuroanatomical mapping and molecular phenotyping of the intracardiac nervous system (ICN). While qualitative and gross anatomical descriptions of the anatomy of the ICN have been presented, we here bring forth the first comprehensive atlas at large scale of the entire ICN in rat at a single cell resolution. Our work for the first time provides a novel 3D model to precisely integrate anatomical, functional and molecular data in the 3D digitally reconstructed whole heart with high resolution at the micron scale. This work represents the cutting edge in a long history of attempts to understand the anatomical substrate upon which the neuronal control of cardiac function is built. To our knowledge, there has not yet been a comprehensive histological mapping to generate a neurocardiac atlas at cellular and molecular level for the whole heart of any species. We now display the full extent and the position of neuronal clusters on the base and posterior left atrium, and the distribution of molecular phenotypes in that context. In addition we display in this context distinct molecular phenotypes that are defined along the base-to-apex axis, and the present novel discovery of their phenotypical spatial gradients, have not been previously described. The development of these approaches needed to acquire these data has produced method pipelines which can not only achieve the goals of anatomical and molecular mapping of the heart, but also provide the method pipelines for mapping other organs (e.g., stomach, lung, kidney, and liver). Comprehensive Neuroanatomy of the Rat HeartHeart tissue sections were imaged as they were cut using a 4th generation KESM platform (Strateos, San Francisco, CA), preserving tissue section morphology and registration to precisely conform to that of the intact, paraffin embedded organ. The image resolution (0.5 µm per pixel) yields clear visualization of cellular/neuronal scale

Autonomic tone in children and adults: Pupillary, electrodermal and cardiac activity at rest

“…This very low frequency has been proposed to reflect mainly PNS influence, sympathovagal balance, renin/angiotensin system (Taylor et al 1998), and other unidentified factors (Billman, 2013). Moreover, we cannot neglect the existence of an intrinsic cardiac nervous system (Achanta et al, 2020;Aksu et al, 2021;Fedele and Brand, 2020;Kerna and Anderson 2021;Shen, 2021), and the influence of neuromodulators or hormones , which challenge the simplistic definition of LF/HF as an index of both SNS and PNS components.…”

Mapping the Organization and Morphology of Calcitonin Gene-Related Peptide (CGRP)-IR Axons in the Whole Mouse Stomach

“…Having these types of information on a scaffold contributes to a more thorough understanding of the organ innervation, as well as making the data more accessible and replicable for other scientists. This is a joint effort from multiple researchers to not only produce the data, but also use the data to navigate 2D connectivity maps and build 3D organ scaffolds that can provide a comprehensive brain-organ atlas and "a common coordinate framework for cross-species comparisons" (Achanta et al 2020, Leung et al 2021.…”