Remodeling of neuronal properties in the preBötzinger Complex (preBötC) causes destabilized rhythm generation following chronic intermittent hypoxia (CIH)

CIH is a cardinal trait of conditions such as apneas of prematurity and sleep apnea. We have previously reported that CIH increases the irregularity of rhythm generation from the preBötC which leads to failed transmission to hypoglossal motor pool. This ongoing study aims to further understand how CIH affects preBötC neurons responsible for premotor generation of the inspiratory rhythm. Electrophysiological studies were conducted in the preBötC of isolated brainstem slices prepared from mice either exposed to room air or to CIH (10 days). Intracellular recordings from synaptically isolated preBötC neurons reveals that CIH exposure causes an increased rheobase and increased threshold for action potential generation. Moreover, in network, preBötC neurons generated fewer action potentials and tended to fire later during the network burst. Computational modeling of the respiratory network suggests that changes in intrinsic properties of preBötC neurons may alter their firing phenotypes (i.e., tonic vs. silent vs. burster). These may lead to relative changes in network composition that destabilizes rhythm generation. We conclude that intrinsic reconfiguration at the neuronal level is necessary for preserving network rhythm generation when experiencing recurrent perturbation such as CIH. Support or Funding Information R01 HL126523; P01 HL090554