Unstable Breathing Rhythms and Quasiperiodicity in the Pre-Bötzinger Complex

Abstract

Breathing in neonatal mammals is notoriously unstable, which can impair normal ventilatory function. Do unstable breathing patterns arise from deterministic mechanisms in the central nervous system? To address this question we examined unstable respiratory patterns using in vitro preparations from neonatal and embryonic rodents that isolate the brain stem kernel containing networks that generate and control breathing’. We also analyzed patterns of ventilation in neonates in vivo and in simulations of rhythm generation using a mathematical model of the kernel². In all of these studies inspiratory rhythms showed evidence of quasiperiodicity, and in some cases the “quasiperiodic transition to chaos” identified in oscillatory dynamical systems by Ruelle and Takens³. In the quasiperiodic regime the inspiratory pattern undergoes amplitude modulation that becomes increasingly disordered and unstable as neuronal excitability is elevated, and leads to chaos-like states of irregular respiratory rhythm. We found that quasiperiodic activity is an intrinsic property of the developing respiratory network that originates in the pre-Bötzinger complex (pre-BötC), the proposed site for respiratory rhythm generation in mammals⁴. Electrophysiological and computational analyses showed that quasiperiodicity can arise in the pre-BötC from rhythm-generating neurons with intrinsic oscillatory bursting-pacemaker properties⁵, thus we identify a potential mechanism for the onset of deterministic respiratory instability in immature mammals.