Fentanyl effects on respiratory neuron activity in the dorsolateral pons

Opioids suppress breathing through actions in the brainstem, including respiratory-related areas of the dorsolateral pons, which contain multiple phenotypes of respiratory patterned neurons. The discharge identity of dorsolateral pontine neurons that are impacted by opioids is unknown. To address this, single neuronal units were recorded in the dorsolateral pons of arterially perfused in situ rat preparations that were perfused with an apneic concentration of the opioid agonist fentanyl, followed by the opioid antagonist naloxone (NLX). Dorsolateral pontine neurons were categorized based on respiratory-associated discharge patterns, which were differentially affected by fentanyl. Inspiratory neurons and a subset of inspiratory/expiratory phase-spanning neurons were either silenced or had reduced firing frequency during fentanyl-induced apnea, which was reversed upon administration of naloxone. In contrast, the majority of expiratory neurons continued to fire tonically during fentanyl-induced apnea, albeit with reduced firing frequency. In addition, pontine late-inspiratory and postinspiratory neuronal activity were absent from apneustic-like breaths during the transition to fentanyl-induced apnea and the naloxone-mediated transition to recovery. Thus, opioid-induced deficits in respiratory patterning may occur due to reduced activity of pontine inspiratory neurons, whereas apnea occurs with loss of all phasic pontine activity and sustained tonic expiratory neuron activity.NEW & NOTEWORTHY Opioids can suppress breathing via actions throughout the brainstem, including the dorsolateral pons. The respiratory phenotype of dorsolateral pontine neurons inhibited by opioids is unknown. Here, we describe the effect of the highly potent opioid fentanyl on the firing activity of these dorsolateral pontine neurons. Inspiratory neurons were largely silenced by fentanyl, whereas expiratory neurons were not. We provide a framework whereby this differential sensitivity to fentanyl can contribute to respiratory pattern deficits and apnea.