Figure 3. Summary of our view of the gross organ ization of respiratory rhythmogenesis in the brainstem of mammals.

We propose that there are two oscillators that are differentially affected by various inputs, such as opiates and lung inflation and deflation. The more rostral oscillator is located in the region of the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) and appears to drive active expiratory activity. It might not be rhythmic in mammals at rest, when there is little or no active expiration. The more caudal oscillator is located in the preBötzinger Complex (preBötC) and appears to drive inspiratory activity. Substance P-saporin (SP-SAP) lesion of preBötC neurokinin 1 receptor (NK1R) neurons disrupts breathing. Transections between the two oscillators disrupt expiratory motor outflow, while inspiratory activity continues unabated. Lung inflation enhances the activity of the expiratory oscillator and depresses the inspiratory oscillator, which serves, ultimately, to reduce lung volume, whereas lung deflation has the opposite effect on the inspiratory and expiratory oscillators. We further speculate that the mechanism of rhythmogenesis in the preBötC involves a group pacemaker. However, this model does not resolve the question of why lesions of the preBötC NK1R neurons in adult rats should disrupt rhythm and render breathing ineffective.