Input-output signal processing plasticity of vagal motor neurons in response to cardiac ischemic injury.

Authors

Jonathan Gorky, Daniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, United StatesFollow
Alison Moss, Daniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, United States
Marina Balycheva, Daniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, United States
Rajanikanth Vadigepalli, Daniel Baugh Institute for Functional Genomics/Computational Biology, Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107, USAFollow
James S. Schwaber, Daniel Baugh Institute for Functional Genomics/Computational Biology, Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107, USAFollow

Document Type

Article

Publication Date

3-19-2021

Comments

This article has been peer reviewed. It was published in: iScience.

Volume 24, Issue 3, 19 March 2021, Article number 102143.

The published version is available at DOI: https://doi.org/10.1016/j.isci.2021.102143

Copyright © 2021 The Authors

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Abstract

Vagal stimulation is emerging as the next frontier in bioelectronic medicine to modulate peripheral organ health and treat disease. The neuronal molecular phenotypes in the dorsal motor nucleus of the vagus (DMV) remain largely unexplored, limiting the potential for harnessing the DMV plasticity for therapeutic interventions. We developed a mesoscale single-cell transcriptomics data from hundreds of DMV neurons under homeostasis and following physiological perturbations. Our results revealed that homeostatic DMV neuronal states can be organized into distinguishable input-output signal processing units. Remote ischemic preconditioning induced a distinctive shift in the neuronal states toward diminishing the role of inhibitory inputs, with concomitant changes in regulatory microRNAs miR-218a and miR-495. Chronic cardiac ischemic injury resulted in a dramatic shift in DMV neuronal states suggestive of enhanced neurosecretory function. We propose a DMV molecular network mechanism that integrates combinatorial neurotransmitter inputs from multiple brain regions and humoral signals to modulate cardiac health.

Recommended Citation

Gorky, Jonathan; Moss, Alison; Balycheva, Marina; Vadigepalli, Rajanikanth; and Schwaber, James S., "Input-output signal processing plasticity of vagal motor neurons in response to cardiac ischemic injury." (2021). Computational Medicine Center Faculty Papers. Paper 33.
https://jdc.jefferson.edu/tjucompmedctrfp/33

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

33665562