Figure 1. Regulation of the cardio-respiratory system by biological CPGs (bCPGs) in the brainstem.

The respiratory bCPG is based on a group of three mutually inhibitory neurons named post-I, aug-E and early-I which generate a three phase rhythm in the following sequence: inspiration (early-I fires), post-inspiration (post-I fires) and expiration (aug-E fires). Pulmonary lung inflation stimulates vagal feedback that inhibits inspiratory neurons. By projecting excitatory synapses to post-I neurons, arterial baroreceptors provide part of the feedback responsible for respiratory sinus arrhythmia. The central coupling between post-I and cardiac vagal motoneurones (cVN) contributes to respiratory sinus arrhythmia (RSA) also. Inspiration is driven by the activation of the pre-I and early-I neurons that via aug-I neurones send signals to inhibit cVN and excite phrenic motoneurones that innervate the diaphragm. cVN activity has the effect of slowing heart rate. This depressive action is balanced by rostral ventrolateral medulla (RVLM) neurons that accelerate heart rate and increase the force of contraction via sympathetic innervation. Figure based on circuits described in Smith et al. 2007 and Smith et al. 2013. Abbreviations: VRC, ventral respiratory group; PN, phrenic nerve; cVN, cardiac vagus nerve; SN, sympathetic nerve; VN, vagus nerve; GPN, glossopharyngeal nerve; RTN, retro-trapezoid nucleus; , excitatory link; , inhibitory link.