Abstract
Current consensus holds that a single medullary network generates respiratory rhythm in mammals. Pre-Bötzinger Complex inspiratory (I) neurons, isolated in transverse slices, and preinspiratory (pre-I) neurons, found only in more intact en bloc preparations and in vivo, are each proposed as necessary for rhythm generation. Opioids slow I, but not pre-I, neuronal burst periods. In slices, opioids gradually lengthened respiratory periods, whereas in more intact preparations, periods jumped nondeterministically to integer multiples of the control period (quantal slowing). These findings suggest that opioid-induced quantal slowing results from transmission failure of rhythmic drive from pre-I neurons to preBötC I networks, depressed below threshold for spontaneous rhythmic activity. Thus, both I (in the slice), and pre-I neurons are sufficient for respiratory rhythmogenesis.
MeSH Terms
Action Potentials/drug effects,physiology
Animals
Biological Clocks/drug effects,physiology
Brain Stem/drug effects,physiology
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology
In Vitro Techniques
Narcotics/pharmacology
Nerve Net/drug effects,physiology
Rats
Receptors, Opioid, mu/agonists,physiology
Respiration/drug effects
Chemicals
Narcotics
Receptors, Opioid, mu
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Mellen Nicholas M
Department of Neurobiology, University of California, Los Angeles, P.O. Box 951763, Los Angeles, CA 90095, USA. nmellen@ucla.edu
Janczewski Wiktor A
Bocchiaro Christopher M
Feldman Jack L
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