Interacting oscillations in neural control of breathing: modeling and qualitative analysis
In mammalian respiration, late-expiratory (late-E, or pre-inspiratory) oscillations emerge in abdominal motor output with increasing metabolic demands (e.g., during hypercapnia, hypoxia, etc.). These oscillations originate in the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) and couple with the respiratory oscillations generated by the interacting neural populations of the Btzinger (BtC) and pre-Btzinger (pre-BtC) complexes, representing the kernel of the respiratory central pattern generator. Recently, we analyzed experimental data on the generation of late-E oscillations and proposed a large-scale computational model that simulates the possible interactions between the BtC/pre-BtC and RTN/pFRG oscillations under different conditions. Here we describe a reduced model that maintains the essential features and architecture of the large-scale model, but relies on simplified activity-based descriptions of neural populations. This simplification allowed us to use methods of dynamical systems theory, such as fast-slow decomposition, bifurcation analysis, and phase plane analysis, to elucidate the mechanisms and dynamics of synchronization between the RTN/pFRG and BtC/pre-BtC oscillations. Three physiologically relevant behaviors have been analyzed: emergence and quantal acceleration of late-E oscillations during hypercapnia, transformation of the late-E activity into a biphasic-E activity during hypercapnic hypoxia, and quantal slowing of BtC/pre-BtC oscillations with the reduction of pre-BtC excitability. Each behavior is elicited by gradual changes in excitatory drives or other model parameters, reflecting specific changes in metabolic and/or physiological conditions. Our results provide important theoretical insights into interactions between RTN/pFRG and BtC/pre-BtC oscillations and the role of these interactions in the control of breathing under different metabolic conditions.
parafacial respiratory group respiratory central pattern generator phase plane analysis neural oscillations pre-btzinger complex coupled oscillators