Affiliation:
1. Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, United States
2. Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, United States
3. RFUMS/DePaul Research Internship Program, Rosalind Franklin University of Medicine and Science, North Chicago, United States
Abstract
How mammalian neural circuits generate rhythmic activity in motor behaviors, such as breathing, walking, and chewing, remains elusive. For breathing, rhythm generation is localized to a brainstem nucleus, the preBötzinger Complex (preBötC). Rhythmic preBötC population activity consists of strong inspiratory bursts, which drive motoneuronal activity, and weaker burstlets, which we hypothesize reflect an emergent rhythmogenic process. If burstlets underlie inspiratory rhythmogenesis, respiratory depressants, such as opioids, should reduce burstlet frequency. Indeed, in medullary slices from neonatal mice, the μ-opioid receptor (μOR) agonist DAMGO slowed burstlet generation. Genetic deletion of μORs in a glutamatergic preBötC subpopulation abolished opioid-mediated depression, and the neuropeptide Substance P, but not blockade of inhibitory synaptic transmission, reduced opioidergic effects. We conclude that inspiratory rhythmogenesis is an emergent process, modulated by opioids, that does not rely on strong bursts of activity associated with motor output. These findings also point to strategies for ameliorating opioid-induced depression of breathing.
Funder
National Institutes of Health
Vetenskapsrådet
Publisher
eLife Sciences Publications, Ltd
Subject
General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience
Cited by
42 articles.
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