Distribution and morphology of calcitonin gene-related peptide and substance P immunoreactive axons in the whole-mount atria of mice

Li, Liang; Hatcher, Jeffrey; Hoover, Donald B.; He, Gu; Wurster, Robert D.; Cheng, Zixi

doi:10.1016/j.autneu.2013.12.010

Cited by 18 publications

(27 citation statements)

References 63 publications

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“…Our investigations in whole mounts have focussed on the subendocardial nerve plexus, whereas previous wholemount studies, in both rats (Richardson et al, 2003) and mice (Rysevaite et al, 2011;Li et al, 2014) have examined the epicardial surface. Intracardiac ganglia (ICG) are found within the epicardial tissue and in rats these form a ring-like plexus around the entry of the pulmonary veins (Richardson et al, 2003).…”

Section: Intrinsic Innervation Of the Atriamentioning

confidence: 99%

Distribution and morphology of sensory and autonomic fibres in the subendocardial plexus of the rat heart

et al. 2020

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Cardiac reflexes originating from sensory receptors in the heart ensure blood supply to vital tissues and organs in the face of constantly changing demands. Atrial volume receptors are mechanically sensitive vagal afferents which relay to the medulla and hypothalamus, affecting vasopressin release and renal sympathetic activity. To date, two anatomically distinct sensory endings have been identified which may subserve cardiac mechanosensation: end-nets and flower-spray endings. To map the distribution of atrial receptors in the subendocardial space, we have double-labelled rat right atrial whole mounts for neurofilament heavy chain (NFH) and synaptic vesicle protein 2 (SV2) and generated high-resolution maps of the rat subendocardial neural plexus at the cavo-atrial region. In order to elucidate the nature of these fibres, double labelling with synaptophysin (SYN) and either NFH, calcitonin gene-related peptide (CGRP), choline acetyltransferase (ChAT) or tyrosine hydroxylase (TH) was performed. The findings show that subendocardial nerve nets are denser at the superior cavo-atrial junction than the mid-atrial region. Adluminal plexuses had the finest diameters and stained positively for synaptic vesicles (SV2 and SYN), CGRP and TH. These plexuses may represent sympathetic post-ganglionic fibres and/or sensory afferents. The latter are candidate substrates for type B volume receptors which are excited by stretch during atrial filling. Deeper nerve fibres appeared coarser and may be cholinergic (positive staining for ChAT). Flower-spray endings were never observed using immunohistochemistry but were delineated clearly with the intravital stain methylene blue. We suggest that differing nerve fibre structures form the basis by which atrial deformation and hence atrial filling is reflected to the brain.

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Section: Intrinsic Innervation Of the Atriamentioning

confidence: 99%

Distribution and morphology of sensory and autonomic fibres in the subendocardial plexus of the rat heart

et al. 2020

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“…In large animals (rabbit, dog, pigs), functional studies showed the two large ganglionic plexuses (GP) of the right atrial ganglionated plexus (RAGP) and the middle pulmonary vein and caudal vena cava (PVCV) may regulate sinoatrial (SA) and atrioventricular (AV) functions to some extent(Allen et al, 2018; Arora et al, 2003; Cardinal et al, 2009; Hardwick et al, 2014; Nakamura et al, 2016; Pauza et al, 2014, 2000; Petraitiene et al, 2014; Saburkina et al, 2014; Singh et al, 2013; Steele et al, 1994; Xi et al, 1991). In rats, two large clusters of ICNS have been reported at similar locations as in the rabbits and pigs, which also regulate the SA heart rate and AV conduction(Ai et al, 2007; Cheng et al, 2004, 1999; Cheng and Powley, 2000; Hoard et al, 2008; Li et al, 2014, 2010; Pauza et al, 2000; Richardson et al, 2003; Rysevaite et al, 2011b, 2011a; Sampaio et al, 2003)\ Our work, mapping out all ICNS neurons, expands upon the concept of ganglionic plexuses with dedicated functional targets by suggesting that while the existence of these GPs may be consistent across individuals and species, the organization of each GP at the single neuron level is highly variable. This organization necessitates annotating the neurons in the ICNS based on how they participate in control of the end organ, not based purely on their location and implies that while the neurons may not be found in the exact same location in every individual, they will have a similar relationship with the potential downstream end-organ targets.…”

Section: Discussionmentioning

confidence: 91%

“…Future normalization of atria after fixation will reveal more similarity of ICNS distribution within and across sexes. However, given the variation of ICNS neuron distribution from the whole-mounts of many carefully prepared male animals, variability between individuals is expected (Li et al, 2014; Rysevaite et al, 2011b, 2011a). Additionally, based on learnings in the present application of PAM, we now are prepared for future studies to further adapt the analysis to consider anatomical features surrounding neuronal clusters in order to partition them without the aid of visual inspection.…”

Section: Discussionmentioning

confidence: 99%

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

Leung

Robbins

Moss

et al. 2020

Preprint

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We developed and analyzed a single cell scale anatomical map of the rat intrinsic cardiac nervous system (ICNS) across 4 male and 3 female hearts. We find the ICNS has a reliable structural organizational plan across individuals that may 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 using 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 in which distinct clusters of neurons are consistently localized. Female hearts had fewer neurons, lower packing density and slightly reduced distribution, but with the same localization. We registered the anatomical data from each heart to a geometric scaffold, normalizing their 3D coordinates for the standardization of common anatomical planes and providing the path where multiple experimental results and data types can be integrated and compared.

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“…The current understanding of ICN is that they modulate cardiac physiological functions of chronotropy, dromotropy, inotropy, and lusitropy. Several anatomical studies have hinted at the complexity of cardiac ganglia organization both in the cell body locations (Hasan, 2013;Hoover et al, 2009;Li et al, 2014;Pauziene et al, 2016;Rysevaite et al, 2011bRysevaite et al, , 2011aSaburkina et al, 2014) and the complexity of afferent and efferent projections to and from the ICN (Cheng et al, 2004(Cheng et al, , 1999Cheng and Powley, 2000;Lin et al, 2014;Li et al, 2014Li et al, , 2010. While some work has hinted at the vast heterogeneity of the ICN from a functional perspective (Beaumont et al, 2013), there has not yet been a systematic assay capable of analyzing the molecular substrates that underlies this functional heterogeneity.…”

Section: Molecular Heterogeneity Of Intrinsic Cardiac Neurons: Functimentioning

confidence: 99%

“…Prior mapping efforts of ICN in small animals have included: mouse (Li et al, 2010(Li et al, , 2014Rysevaite et al, 2011a), rat (Ai et al, 2007;Cheng et al, 1999Cheng et al, , 2004Cheng and Powley, 2000), rabbit (Saburkina et al, 2014), guinea pig (Hardwick et al, 2014;Steele et al, 1994). Some of these prior efforts provided limited mapping.…”

Section: Introductionmentioning

confidence: 99%

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

Achanta

Gorky

Leung

et al. 2019

Preprint

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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

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Distribution and morphology of calcitonin gene-related peptide and substance P immunoreactive axons in the whole-mount atria of mice

Cited by 18 publications

References 63 publications

Distribution and morphology of sensory and autonomic fibres in the subendocardial plexus of the rat heart

Distribution and morphology of sensory and autonomic fibres in the subendocardial plexus of the rat heart

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

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

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