Determinants of inspiratory activity.

In vitro and in vivo studies have identified the pre-Bötzinger complex as an important kernel for the generation of inspiratory activity. The mechanisms underlying inspiratory rhythm generation involve pacemaker as well as synaptic mechanisms. In slice preparations, blockade of pacemaker properties with blockers for the persistent Na+ current, and the Ca2+-activated inward cationic current, abolishes respiratory activity. Here we show that blockade of the persistent Na+ current alone is sufficient to abolish respiratory activity in the in situ preparation. Although pacemaker neurons may be critical for establishing the basic respiratory rhythm, their rhythmic output is modulated by many elements of the respiratory network. For example, levels of synaptic inhibition control whether they burst or not, and endogenously released neuromodulators, such as serotonin and substance P modulate their intrinsic membrane currents. We hypothesize that the balance between synaptic and intrinsic pacemaker properties in the respiratory network is plastic, and that alterations of this balance may lead to dynamic reconfigurations of the respiratory network, which ultimately give rise to different activity patterns.