Input-output signal processing plasticity of vagal motor neurons in response to cardiac ischemic injury
Summary: 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 plast...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-03-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221001115 |
| _version_ | 1818677443379068928 |
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| author | Jonathan Gorky Alison Moss Marina Balycheva Rajanikanth Vadigepalli James S. Schwaber |
| author_facet | Jonathan Gorky Alison Moss Marina Balycheva Rajanikanth Vadigepalli James S. Schwaber |
| author_sort | Jonathan Gorky |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-12-17T08:59:27Z |
| format | Article |
| id | doaj.art-0cbfdd2f520e45ca88e2764880bebbec |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-17T08:59:27Z |
| publishDate | 2021-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-0cbfdd2f520e45ca88e2764880bebbec2022-12-21T21:55:47ZengElsevieriScience2589-00422021-03-01243102143Input-output signal processing plasticity of vagal motor neurons in response to cardiac ischemic injuryJonathan Gorky0Alison Moss1Marina Balycheva2Rajanikanth Vadigepalli3James S. Schwaber4Daniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USADaniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USADaniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USADaniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA; Corresponding authorDaniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004221001115Molecular PhysiologyNeuroscienceTranscriptomics |
| spellingShingle | Jonathan Gorky Alison Moss Marina Balycheva Rajanikanth Vadigepalli James S. Schwaber Input-output signal processing plasticity of vagal motor neurons in response to cardiac ischemic injury iScience Molecular Physiology Neuroscience Transcriptomics |
| title | Input-output signal processing plasticity of vagal motor neurons in response to cardiac ischemic injury |
| title_full | Input-output signal processing plasticity of vagal motor neurons in response to cardiac ischemic injury |
| title_fullStr | Input-output signal processing plasticity of vagal motor neurons in response to cardiac ischemic injury |
| title_full_unstemmed | Input-output signal processing plasticity of vagal motor neurons in response to cardiac ischemic injury |
| title_short | Input-output signal processing plasticity of vagal motor neurons in response to cardiac ischemic injury |
| title_sort | input output signal processing plasticity of vagal motor neurons in response to cardiac ischemic injury |
| topic | Molecular Physiology Neuroscience Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221001115 |
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