Year: 2019
Type: article
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.
Source: eLife
DOI: 10.7554/elife.50613
Authors: Xiaolu Sun, Carolina Thörn Pérez, Halemani D Nagaraj, Xuesi M. Shao, Morgan Greenwood, Sarah Heath, Jack L. Feldman, Kaiwen Kam
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: Center for Study of Opioid Receptors and Drugs of Abuse (CSORDA), The role of inhibitory microcircuits in the neural control of breathing, Maternal inhaled nicotine leads to aberrant development of hypertensive phenotype, Functional Dissection of Medullary Respiratory Microcircuits, Neural control of breathing, G5309717914, G9000334676, G9000339155
OpenAlex ID: W2995388315