IMR Press / JIN / Volume 19 / Issue 3 / DOI: 10.31083/j.jin.2020.03.0196
Retraction published on 30 June 2021, see Journal of Integrative Neuroscience 2021, 20(2)
Open Access Review
Mechanisms underlying the generation of autonomorespiratory coupling amongst the respiratory central pattern generator, sympathetic oscillators, and cardiovagal premotoneurons
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1 Department of Neurological Surgery, Karolinska Institutet, Nobels väg 6 Solna and Alfred Nobels Allé 8 Huddinge SE-171 77, Stockholm, Sweden
2 Department of Neurological Surgery, University of Helsinki, 00100, Helsinki, Finland
3 Department of Neurological Surgery, University of Oslo, P.O. Box 1076 Blindern, N-0316 Oslo, Norway
4 Department of Neurological Surgery, University of California San Francisco, 505 Parnassus Street, San Francisco, CA, 94143, USA
5 Department of Neurological Surgery, Barrow Neurological Institute, 350 W. Thomas Road, Phoenix, Arizona, 85013, USA
6 Department of Neurosurgery, University Hospital, Zurich, Rämistrasse Zurich, 100, 8091, Switzerland
7 Purdue University, 610 University Mall, West Lafayette, IN, 47907, USA
8 United States Environmental Protection Agency, 2777 Crystal Drive, Arlington, VA 22202
9 Department of Neurological Surgery, University of Barcelona, Gran Via de les Corts Catalanes, Barcelona, 585 08007, Spain
10 Department of Neurological Surgery, Oxford University, Oxford OX1, Oxford, United Kingdom
11 Department of Neurological Surgery, Cambridge University, 184 Hills Road, Cambridge CB2 8PQ United Kingdom
12 Department of Neurosurgery, Johns Hopkins Medical Institute, 1800 Orleans Street, Baltimore, MD 21287, USA
*Correspondence: (Michael G. Z. Ghali)
J. Integr. Neurosci. 2020, 19(3), 521–560;
Submitted: 28 June 2019 | Revised: 2 December 2019 | Accepted: 4 December 2019 | Published: 30 September 2020
Copyright: © 2020 Ghali et al. Published by IMR Press.
This is an open access article under the CC BY 4.0 license (

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 sympathetic- and respiratory-related central neuronal and efferent neurogram recordings and quantified by the findings of cross-correlation, 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.

rostral ventrolateral medulla
Fig. 1.
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