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Looking for inspiration: new perspectives on respiratory rhythm

Abstract

Recent experiments in vivo and in vitro have advanced our understanding of the sites and mechanisms involved in mammalian respiratory rhythm generation. Here we evaluate and interpret the new evidence for two separate brainstem respiratory oscillators and for the essential role of emergent network properties in rhythm generation. Lesion studies suggest that respiratory cell death might explain morbidity and mortality associated with neurodegenerative disorders and ageing.

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Figure 1: Ventral view of en bloc brainstem showing voltage-dependent respiratory neuronal activity.
Figure 2: Opiate agonists induce quantal slowing of inspirations without affecting frequency of active expirations.
Figure 3: Summary of our view of the gross organ<>ization of respiratory rhythmogenesis in the brainstem of mammals.
Figure 4: Lesions of the preBötzinger Complex significantly disturb breathing pattern in an unrestrained, unanaesthetized adult rat.
Figure 5: Group-pacemaker hypothesis of respiratory rhythm generation.

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Acknowledgements

The authors thank G. F. Alheid and D. R. McCrimmon of Northwestern University, Illinois, USA, for the figures and for editing the text in Box 2. We thank our colleagues in the Systems Neurobiology Laboratory at the University of California, Los Angeles, USA, for their incisive comments on earlier versions of this manuscript. This work was supported by grants from the National Institutes of Health, USA, the Jeffress Memorial Trust, Richmond, Virginia, USA, and the Parker B. Francis Fellowship in Pulmonary Research, Parker B. Francis Foundation, Kansas City, Missouri, USA.

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DATABASES

OMIM

Amyotrophic lateral sclerosis

Congenital central hypoventilation syndrome

Parkinson's disease

Rett syndrome

Sudden infant death syndrome

Entrez gene

Krox20

MafB

MeCP2

NK1R

Glossary

Rett syndrome

Mutation of the MeCP2 gene on the Xchromosome causes irregular breathing patterns during wakefulness and motor control deficits.

Ondines curse

(Also known as congenital central hypoventilation syndrome). Characterized by episodes of sleep apnoea starting at birth that lead to pathophysiological respiration.

Amyotrophic lateral sclerosis

(ALS; also known as Lou Gehrigs disease). A neurodegenerative disorder characterized by progressive motor neuronal cell death and severe muscular atrophy.

Multiple systems atrophy

(MSA). A neurodegenerative disease of undetermined aetiology encompassing several clinical syndromes including (but not limited to) parkinsonism and autonomic dysfunction.

Ataxia

Uncoordinated muscular movements symptomatic of some nervous disorders or pathological conditions.

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Feldman, J., Del Negro, C. Looking for inspiration: new perspectives on respiratory rhythm. Nat Rev Neurosci 7, 232–241 (2006). https://doi.org/10.1038/nrn1871

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