Mechanisms underlying the generation of autonomorespiratory coupling amongst the respiratory central pattern generator, sympathetic oscillators, and cardiovagal premotoneurons

Michael G.Z. Ghali, George Zaki Ghali, Adriana Lima, Michael McDermott, Emma Glover, Stefanos Voglis, Jennifer Humphrey, Marton Skog Steinberger König, Henry Brem, Per Uhlén, Robert F. Spetzler, M. Gazi Yasargil

Research output: Contribution to journalArticlepeer-review


The respiratory rhythm and pattern and sympathetic and parasympathetic outflows are generated by distinct, though overlapping, propriobulbar arrays of neuronal microcircuit oscillators constituting networks utilizing mutual excitatory and inhibitory neuronal interactions, residing principally within the metencephalon and myelencephalon, and modulated by synaptic influences from the cerebrum, thalamus, hypothalamus, cerebellum, and mesencephalon and ascending influences deriving from peripheral stimuli relayed by cranial nerve afferent axons. Though the respiratory and cardiovascular regulatory effector mechanisms utilize distinct generators, there exists significant overlap and interconnectivity amongst and between these oscillators and pathways, evidenced reciprocally by breathing modulation of sympathetic oscillations and sympathetic modulation of neural breathing. These coupling mechanisms are well-demonstrated coordinately in sympatheticand respiratory-related central neuronal and efferent neurogram recordings and quantified by the findings of crosscorrelation, spectra, and coherence analyses, combined with empirical interventions including lesioning and pharmacological agonist and antagonist microinjection studies, baroloading, barounloading, and hypoxic and/or hypercapnic peripheral and/or central chemoreceptor stimulation. Sympathetic and parasympathetic central neuronal and efferent neural discharge recordings evidence classic fast rhythms produced by propriobulbar neuronal networks located within the medullary division of the lateral tegmental field, coherent with cardiac sympathetic nerve discharge. These neural efferent nerve discharges coordinately evidence slow synchronous oscillations, constituted by Traube Hering (i.e., high frequency), Mayer wave (i.e., medium or low frequency), and vasogenic autorhythmicity (i.e., very low frequency) wave spectral bands. These oscillations contribute to coupling neural breathing, sympathetic oscillations, and parasympathetic cardiovagal premotoneuronal activity. The mechanisms underlying the origins of and coupling amongst, these waves remains to be unresolved.

Original languageEnglish (US)
Pages (from-to)521-560
Number of pages40
JournalJournal of Integrative Neuroscience
Issue number3
StatePublished - Sep 30 2020
Externally publishedYes


  • Cardiovagal
  • Coupling
  • Genesis
  • Hypercapnia
  • Hypoxia
  • Mechanisms
  • Modulation
  • Rostral ventrolateral medulla
  • Sympathetic
  • Sympathorespiratory

ASJC Scopus subject areas

  • Neuroscience(all)


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