The circuit organization within the mammalian brainstem respiratory network, specifically within and between the pre-Bxc3xb6tzinger (pre-Bxc3xb6tC) and Bxc3xb6tzinger (Bxc3xb6tC) complexes, and the roles of these circuits in respiratory pattern generation are continuously debated. We address these issues with a combination of optogenetic experiments and modeling studies. We used transgenic mice expressing channelrhodopsin-2 under the VGAT-promoter to investigate perturbations of respiratory circuit activity by site-specific photostimulation of inhibitory neurons within the pre-Bxc3xb6tC or Bxc3xb6tC. The stimulation effects were dependent on the intensity and phase of the photostimulation. Specifically: (1) Low intensity (xe2x89xa4 1.0 mW) pulses delivered to the pre-Bxc3xb6tC during inspiration did not terminate activity, whereas stronger stimulations (xe2x89xa5 2.0 mW) terminated inspiration. (2) When the pre-Bxc3xb6tC stimulation ended in or was applied during expiration, rebound activation of inspiration occurred after a fixed latency. (3) Relatively weak sustained stimulation (20 Hz, 0.5-2.0 mW) of pre-Bxc3xb6tC inhibitory neurons increased respiratory frequency, while a further increase of stimulus intensity (> 3.0 mW) reduced frequency and finally (xe2x89xa5 5.0 mW) terminated respiratory oscillations. (4) Single pulses (0.2-5.0 s) applied to the Bxc3xb6tC inhibited rhythmic activity for the duration of the stimulation. (5) Sustained stimulation (20 Hz, 0.5-3.0 mW) of the Bxc3xb6tC reduced respiratory frequency and finally led to apnea. We have revised our computational model of pre-Bxc3xb6tC and Bxc3xb6tC microcircuits by incorporating an additional population of post-inspiratory inhibitory neurons in the pre-Bxc3xb6tC that interacts with other neurons in the network. This model was able to reproduce the above experimental findings as well as previously published results of optogenetic activation of pre-Bxc3xb6tC or Bxc3xb6tC neurons obtained by other laboratories. The proposed organization of pre-Bxc3xb6tC and Bxc3xb6tC circuits leads to testable predictions about their specific roles in respiratory pattern generation and provides important insights into key circuit interactions operating within brainstem respiratory networks.