Central respiratory oscillator: phase-response analysis.

To investigate properties of the central respiratory oscillator, phrenic nerve activity, perturbed by electrical stimulation of the middle external intercostal nerve, was analyzed in rabbit by using a phase-response curve (PRC). During inspiration, the stimuli (4-8 pulses) caused all-or-none responses, i.e. a phase advance or no phase shift, and strong stimuli (10 pulses) induced only phase advances. During expiration only graded phase delays were observed. The overall slope of PRC was 0 for 2 pulses and 1 for 10 pulses. At the transition from expiration (E) to inspiration (I), the PRC was discontinuous. This discontinuity corresponds to a phase singularity. In contrast, at the transition from I to E, the PRC was continuous. Therefore, our findings indicate that E-I switching may differ from I-E switching in nature. The respiratory rhythm could not be stopped by perturbation at the phase singularity as predicted from the PRCs. Similarities between the reported PRCs, obtained by inhibitory stimulation of an endogenous bursting neuron and the PRCs in the present study, suggest a possibility that endogenous bursting neurons take part in the function of a mammalian central respiratory oscillator.