Analyse de la contribution des oscillateurs centraux commandant la ventilation à la non linéarité et à la complexité de sa dynamique

Human ventilation is not a regular, phenomenon. It follows a nonlinear complex trajectory and exhibits mathematical chaos-like features. Available data suggest that ventilatory complexity arises from the automatic breathing command. It depends on two separate but interacting brainstem oscillators: the pre-Botzinger complex (preBotC) and the parafacial respiratory group (pFRG), closely related to the retro-trapezoid nucleus (RTN). The neural respiratory output of brainstems, isolated from post-metamorphic tadpoles, shares the same properties. The latter model displays two ventilatory motor patterns: the buccal and the lung rhythms. They depend at least on two distinct oscillators. The homology of the lung oscillator and the preBotC, and of the buccal oscillator and the RTN/pFRG has been suggested. This thesis shows that the lung oscillator is both necessary and sufficient to the ventilatory complexity of the post-metamorphic tadpole. Mice bearing the mutation of the Phox2b gene that causes congenital central hypoventilation syndrome (CCHS) in humans exhibited the same respiratory phenotype and lacked the neurons that characterize the pFRG/RTN. Their ventilation exhibits nonlinearity and complexity. Thus, the pFRG is not necessary to the emergence of this complexity in mice. The preBotC could be a sufficient source. Assuming that the RTN/pFRG neurons are also missing in CCHS patients, only the preBotC would be active. Ventilation in patient displays nonlinear chaos-like complexity. Therefore the pFRG/RTN is likely not necessary to this complexity in human. The preBotC may be a sufficient source, though the role of other afferents or cerebral structures cannot be excluded