Figure 5. Group-pacemaker hypothesis of respiratory rhythm generation.

The membrane potential of a rhythm-generating neuron is shown (V_M, top trace) with network activity, represented by XII motor output (XII, bottom). Images to the right of the traces depict neuronal activity at different stages of the cycle. 1 is the refractory state that follows inspiration, in which activity-dependent outward currents depress membrane potential, and excitatory synapses in the network are inactive. During epoch 2, the most excitable neurons recover from post-burst hyperpolarization and begin to spike at a low rate. By 3 these highly excitable cells begin to synaptically activate other neurons, leading to aggregation of network activity itself due to recurrent synaptic excitation — a positive-feedback process. The inspiratory burst (4) ensues once a critical number of cells in the network are activated by recurrent excitation. In this final step, synaptic inputs recruit burst-generating intrinsic currents such as Ca²⁺-activated nonspecific cationic current (I_CAN) and persistent Na⁺ current (I_NaP), which give rise to large inspiratory burst potentials with high-frequency spike activity. Inspiratory bursts terminate owing to intrinsic properties of cells that can reverse the positive feedback process, including Ca²⁺-dependent K⁺ currents and electrogenic pumps, which are recruited by cationic influx during inspiration.