Unpacking the multimodal, multi-scale data of the fast and slow lanes of the cardiac vagus through computational modelling
| Author(s) | Gee, Michelle M. | |
| Author(s) | Hornung, Eden | |
| Author(s) | Gupta, Suranjana | |
| Author(s) | Newton, Adam J. H. | |
| Author(s) | Cheng, Zixi (Jack) | |
| Author(s) | Lytton, William W. | |
| Author(s) | Lenhoff, Abraham M. | |
| Author(s) | Schwaber, James S. | |
| Author(s) | Vadigepalli, Rajanikanth | |
| Date Accessioned | 2023-08-10T19:09:21Z | |
| Date Available | 2023-08-10T19:09:21Z | |
| Publication Date | 2023-04-30 | |
| Description | This article was originally published in Experimental Physiology. The version of record is available at: https://doi.org/10.1113/EP090865. ©2023 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. | |
| Abstract | New Findings What is the topic of this review? The vagus nerve is a crucial regulator of cardiovascular homeostasis, and its activity is linked to heart health. Vagal activity originates from two brainstem nuclei: the nucleus ambiguus (fast lane) and the dorsal motor nucleus of the vagus (slow lane), nicknamed for the time scales that they require to transmit signals. What advances does it highlight? Computational models are powerful tools for organizing multi-scale, multimodal data on the fast and slow lanes in a physiologically meaningful way. A strategy is laid out for how these models can guide experiments aimed at harnessing the cardiovascular health benefits of differential activation of the fast and slow lanes. The vagus nerve is a key mediator of brain–heart signaling, and its activity is necessary for cardiovascular health. Vagal outflow stems from the nucleus ambiguus, responsible primarily for fast, beat-to-beat regulation of heart rate and rhythm, and the dorsal motor nucleus of the vagus, responsible primarily for slow regulation of ventricular contractility. Due to the high-dimensional and multimodal nature of the anatomical, molecular and physiological data on neural regulation of cardiac function, data-derived mechanistic insights have proven elusive. Elucidating insights has been complicated further by the broad distribution of the data across heart, brain and peripheral nervous system circuits. Here we lay out an integrative framework based on computational modelling for combining these disparate and multi-scale data on the two vagal control lanes of the cardiovascular system. Newly available molecular-scale data, particularly single-cell transcriptomic analyses, have augmented our understanding of the heterogeneous neuronal states underlying vagally mediated fast and slow regulation of cardiac physiology. Cellular-scale computational models built from these data sets represent building blocks that can be combined using anatomical and neural circuit connectivity, neuronal electrophysiology, and organ/organismal-scale physiology data to create multi-system, multi-scale models that enable in silico exploration of the fast versus slow lane vagal stimulation. The insights from the computational modelling and analyses will guide new experimental questions on the mechanisms regulating the fast and slow lanes of the cardiac vagus toward exploiting targeted vagal neuromodulatory activity to promote cardiovascular health. | |
| Sponsor | Authors acknowledge funding received from National Heart, Lung, and Blood Institute (NHLBI): J.S., R.V., U01 HL133360; R01 HL161696; National Institutes of Health (NIH): W.W.L., J.S., R.V., OT2 OD030534; National Science Foundation (NSF): M.G., 1940700. The funders had no role in the study design, analysis and interpretation and drafting of the manuscript. | |
| Citation | Gee, M. M., Hornung, E., Gupta, S., Newton, A. J. H., Cheng, Z. (J.), Lytton, W. W., Lenhoff, A. M., Schwaber, J. S., & Vadigepalli, R. (2023). Unpacking the multimodal, multi-scale data of the fast and slow lanes of the cardiac vagus through computational modelling. Experimental Physiology, 00, 1–7. https://doi.org/10.1113/EP090865 | |
| ISSN | 1469-445X | |
| URL | https://udspace.udel.edu/handle/19716/33061 | |
| Language | en_US | |
| Publisher | Experimental Physiology | |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
| Keywords | cardiovascular control | |
| Keywords | computational neuroscience | |
| Keywords | mathematical model | |
| Keywords | vagus nerve | |
| Title | Unpacking the multimodal, multi-scale data of the fast and slow lanes of the cardiac vagus through computational modelling | |
| Type | Article |
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