| Pacemakers handshake synchronization mechanism of mammalian respiratory rhythmogenesis. | |
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MedLine Citation:
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PMID: 19008356 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Inspiratory and expiratory rhythms in mammals are thought to be generated by pacemaker-like neurons in 2 discrete brainstem regions: pre-Bötzinger complex (preBötC) and parafacial respiratory group (pFRG). How these putative pacemakers or pacemaker networks may interact to set the overall respiratory rhythm in synchrony remains unclear. Here, we show that a pacemakers 2-way "handshake" process comprising pFRG excitation of the preBötC, followed by reverse inhibition and postinhibitory rebound (PIR) excitation of the pFRG and postinspiratory feedback inhibition of the preBötC, can provide a phase-locked mechanism that sequentially resets and, hence, synchronizes the inspiratory and expiratory rhythms in neonates. The order of this handshake sequence and its progression vary depending on the relative excitabilities of the preBötC vs. the pFRG and resultant modulations of the PIR in various excited and depressed states, leading to complex inspiratory and expiratory phase-resetting behaviors in neonates and adults. This parsimonious model of pacemakers synchronization and mutual entrainment replicates key experimental data in vitro and in vivo that delineate the developmental changes in respiratory rhythm from neonates to maturity, elucidating their underlying mechanisms and suggesting hypotheses for further experimental testing. Such a pacemakers handshake process with conjugate excitation-inhibition and PIR provides a reinforcing and evolutionarily advantageous fail-safe mechanism for respiratory rhythmogenesis in mammals. |
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Authors:
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Steffen Wittmeier; Gang Song; James Duffin; Chi-Sang Poon |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-11-13 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 105 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2008 Nov |
Date Detail:
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Created Date: 2008-11-21 Completed Date: 2008-12-17 Revised Date: 2010-09-23 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 18000-5 Citation Subset: IM |
Affiliation:
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Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analgesics, Opioid
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pharmacology Animals Animals, Newborn Biological Clocks / drug effects, physiology* Computer Simulation Mammals / physiology* Models, Neurological* Respiration* / drug effects Respiratory Center / drug effects, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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EB005460/EB/NIBIB NIH HHS; HL067966/HL/NHLBI NIH HHS; HL072849/HL/NHLBI NIH HHS; HL079503/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Analgesics, Opioid |
| Comments/Corrections | |
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