Abstract
The intracardiac nervous system (IcNS), sometimes referred to as the “little brain” of the heart, is involved in modulating many aspects of cardiac physiology. In recent years our fundamental understanding of autonomic control of the heart has drastically improved, and the IcNS is increasingly being viewed as a therapeutic target in cardiovascular disease. However, investigations of the physiology and specific roles of intracardiac neurons within the neural circuitry mediating cardiac control has been hampered by an incomplete knowledge of the anatomical organisation of the IcNS. A more thorough understanding of the IcNS is hoped to promote the development of new, highly targeted therapies to modulate IcNS activity in cardiovascular disease. In this paper, we first provide an overview of IcNS anatomy and function derived from experiments in mammals. We then provide descriptions of alternate experimental models for investigation of the IcNS, focusing on a non-mammalian model (zebrafish), neuron-cardiomyocyte co-cultures, and computational models to demonstrate how the similarity of the relevant processes in each model can help to further our understanding of the IcNS in health and disease.
Highlights
We follow this with a description of alternative experimental models, focusing on zebrafish, cell culture, and computational models, to highlight how investigations using these models can further our understanding of intracardiac nervous system (IcNS) structure and function
While mammalian studies of the IcNS have long been mainstays of the field, the size of the heart and nature of the IcNS in these models has resulted in studies utilising reduced preparations, with truncated network connections, which has limited integrative insight
Zebrafish offer many advantages, including observation of in vivo and developmental aspects not possible in mammalian models, the basic anatomy and physiology of the zebrafish means that caution should be exercised in extrapolating results to mammals
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. In the traditional model of cardiac regulation, the central nervous system (CNS), encompassing the spinal cord, medulla, and higher brain centres, processes cardiovascular feedback, and relays signals to the heart via peripheral ANS nerves. In this configuration, the IcNS is a conduit for central inputs to the heart [8,11]. We provide a brief overview of the knowledge derived from mammalian models (e.g., porcine, canine, and murine) and considerations for their use We follow this with a description of alternative experimental models, focusing on zebrafish, cell culture, and computational models, to highlight how investigations using these models can further our understanding of IcNS structure and function
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