Driving respiration: the respiratory central pattern generator.

1. The central pattern generator (CPG) for respiration is located in the brainstem and produces rhythmic synaptic drive for motoneurons controlling respiratory muscles. Based on respiratory nerve discharge, the respiratory cycle can be divided into three phases: inspiration, postinspiration and stage 2 expiration. 2. Six basic types of respiratory neuron participate in respiratory rhythmogenesis. Their firing and membrane potential patterns are locked to different phases of the respiratory cycle. 3. In adult mammals, respiratory neurons are subject to excitatory and inhibitory synaptic inputs and show extensive synaptic interconnections that are mainly inhibitory. There are differences in the relative importance of excitatory and inhibitory synaptic drives and the neurotransmitters involved in respiratory rhythmogenesis in neonates compared with adults. 4. Respiratory neurons possess a number of intrinsic membrane currents that may be involved in central pattern generation, including low- and high-voltage-activated calcium, potassium, calcium-dependent potassium, sodium and mixed cationic currents. More quantitative information is needed about the distribution and characteristics of these ionic currents if we are to understand rhythmogenesis. 5. The two main theories for the origin of respiratory rhythm are those of pacemaker neuron-driven and synaptic network-driven CPG. Evidence derived from in vivo and in vitro experiments exists to support both of these theories. There may be a significant switch in the underlying mechanism driving the respiratory CPG during postnatal development.