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Anatomical characterization of vagal nodose afferent innervation and ending morphologies at the murine heart using a transgenic approach

  • Author Footnotes
    1 Equal contribution.
    Yusuf Enes Kazci
    Footnotes
    1 Equal contribution.
    Affiliations
    Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, 34810 Istanbul, Turkey

    Istanbul Medipol University, Institute of Health Sciences, Neuroscience Program, Istanbul, Turkey

    Deparment of Medical Biology, International School of Medicine, Istanbul Medipol University, Istanbul, Turkey
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  • Author Footnotes
    1 Equal contribution.
    Sevilay Sahoglu Goktas
    Footnotes
    1 Equal contribution.
    Affiliations
    Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, 34810 Istanbul, Turkey

    Istanbul Medipol University, Institute of Health Sciences, Neuroscience Program, Istanbul, Turkey

    Department of Medical Biology, School of Medicine, Istanbul Medipol University, Istanbul, Turkey
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  • Mehmet Serif Aydin
    Affiliations
    Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, 34810 Istanbul, Turkey
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  • Behnaz Karadogan
    Affiliations
    Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, 34810 Istanbul, Turkey
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  • Aylin Nebol
    Affiliations
    Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, 34810 Istanbul, Turkey

    Istanbul Medipol University, Institute of Health Sciences, Medical Biology and Genetics Graduate Program, Istanbul, Turkey
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  • Mehmet Ugurcan Turhan
    Affiliations
    Cerrahpasa Medical School, Department of Cardiovascular Surgery, Istanbul University, Istanbul, Turkey
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  • Gurkan Ozturk
    Affiliations
    Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, 34810 Istanbul, Turkey

    Istanbul Medipol University, Institute of Health Sciences, Neuroscience Program, Istanbul, Turkey

    Physiology Department, International School of Medicine, Istanbul Medipol University, 34810 Istanbul, Turkey
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  • Esra Cagavi
    Correspondence
    Corresponding author at: Department of Medical Biology, School of Medicine, Institute of Health Sciences, Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, 34810 Istanbul, Turkey.
    Affiliations
    Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, 34810 Istanbul, Turkey

    Deparment of Medical Biology, International School of Medicine, Istanbul Medipol University, Istanbul, Turkey

    Department of Medical Biology, School of Medicine, Istanbul Medipol University, Istanbul, Turkey

    Istanbul Medipol University, Institute of Health Sciences, Medical Biology and Genetics Graduate Program, Istanbul, Turkey
    Search for articles by this author
  • Author Footnotes
    1 Equal contribution.

      Highlights

      • Cardiac vagal afferents at Phox2b-Cre::tdTomato mouse whole heart were mapped in high resolution.
      • Flower spray and end-net-like endings were detected at vagal afferents within the atria and ventricles.
      • Vagal afferents formed intramuscular array-like endings exclusively within the ventricles.
      • Vagal afferents undergo structural remodeling around the infarct area in post-MI hearts.

      Abstract

      Heart is an extensively innervated organ and its function is strictly coordinated by autonomic neural circuits. After pathological events such as myocardial infarction (MI), cardiac nerves undergo a structural and functional remodeling contributing to cardiac dysfunction. Although the efferent component of the cardiac nerves has been well described, sensory innervation of the heart has not been defined in detail. Considering its importance, comprehensive description of vagal afferent innervation on the whole heart would enable a better description of autonomic imbalances manifesting as sympathoexcitation and vagal withdrawal in post-ischemic states. To address this issue, we globally mapped the vagal nodose afferent fibers innervating the whole murine heart with unprecedented resolution. By using the Phox2b-Cre::tdTomato transgenic mouse line, we described the detailed distribution and distinct vagal sensory ending morphologies at both the dorsal and ventral sides of the mouse heart. By neural tracing analysis, we quantitated the distribution and prevalence of vagal afferent nerve fibers with varying diameters across dorsal and ventral surfaces of the heart. Moreover, we demonstrated that vagal afferents formed flower spray and end-net-like endings within the atria and ventricles. As distinct from the atria, vagal afferents formed intramuscular array-like endings within the ventricles. Furthermore, we showed that vagal afferents undergo structural remodeling by forming axonal sprouts around the infarct area in post-MI hearts. These findings improve our understanding of the potential effect of vagal afferent remodeling on autonomic imbalance and generation of cardiac arrhythmias and could prospectively contribute to the development of more effective neuromodulatory therapies.

      Keywords

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