Investigating inhibitory synaptic transmission in developing Kölliker-Fuse neurons from mu opioid receptor knock-out mice

After nine months in the aqueous uterine environment, a newborn’s first breath of air is a major transition for the respiratory system. Newborn breathing is slow and is often interspersed with apneas. Premature infants can have dangerously impaired breathing with apneas causing oxygen desaturation and death. Administration of the non-selective opioid receptor antagonist naloxone increases breathing rate in neonatal mammals including human infants. Therefore, I hypothesized that endogenous opioid peptides suppress breathing during early life. To test this hypothesis, I measured breathing in mice lacking mu-opioid receptors (MOR-KO) and wild type littermate mice at multiple developmental time points. At P0 and P21, MOR-KO mice breathed faster than wild types. These results suggest that P0 and P21 are critical windows for endogenous opioid regulation of breathing rate in mice. The pontine Kölliker-Fuse (KF) area contains essential breathing control neurons that regulate respiratory rate, in addition to other functions in breathing control. The KF is known to undergo substantial postnatal maturation in rats. Therefore, we hypothesized that the deletion of MORs alters the physiology of developing KF neurons in mice. To test this, we performed brain slice electrophysiology experiments in KF neurons from MOR-KO and wild type mice at different developmental time points. Preliminary data show developmental shifts in the decay kinetics of spontaneous inhibitory postsynaptic currents in wild type mice and MOR-KO mice. Regardless of genotype, spontaneous inhibitory postsynaptic currents recorded from P7-8 mice exhibit slower decay kinetics than those recorded in mice older than P14. These data suggest that the maturational shift in inhibitory synaptic transmission occurs independent of mu opioid receptor expression. Understanding the fundamental role of mu opioid receptors in pontine respiratory neuron development will help determine the physiological mechanisms defining the critical windows of endogenous opioid influence on breathing at birth and weaning. Acknowledgements: This research was supported by K99 HL177177 and T32 DA060142 to JWF and R01 HL174547 to ESL. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.