| First Author | Sun X | Year | 2019 |
| Journal | Elife | Volume | 8 |
| PubMed ID | 31841107 | Mgi Jnum | J:284534 |
| Mgi Id | MGI:6390681 | Doi | 10.7554/eLife.50613 |
| Citation | Sun X, et al. (2019) Opioids modulate an emergent rhythmogenic process to depress breathing. Elife 8:e50613 |
| abstractText | 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 preBotzinger Complex (preBotC). Rhythmic preBotC 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 mu-opioid receptor (muOR) agonist DAMGO slowed burstlet generation. Genetic deletion of muORs in a glutamatergic preBotC 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. |
