Contribution of pacemaker neurons to respiratory rhythms generation in vitro

Neurons with pacemaker properties have been described in several neural networks. Nonlinearity of their bursting activity might enable them to facilitate onset of excitatory states or to synchronize neuronal ensembles. However, whether such neurons are essential for generating a network activity pattern remains mostly unknown. For the mammalian respiratory network, located in the preBötzinger complex (PBC), two types of pacemaker neurons have been described. Bursting properties of one type of pacemakers rely on the riluzole-sensitive persistent sodium current, whereas bursting mechanisms of a second type are sensitive to Cd2+ and flufenamic acid, a calcium-dependent nonspecific cationic current blocker. The role of pacemakers in the generation of respiratory rhythms in vitro is state dependent. Under control conditions, the respiratory network generates fictive eupneic activity; this activity depends on both riluzole-sensitive and flufenamic acid-sensitive pacemakers. During hypoxia, fictive eupneic activity is supplanted by the neural correlate of gasping and only riluzole-sensitive pacemaker neurons appear to be necessary for this rhythm. Thus, at least two types of pacemaker bursting mechanisms are present in the PBC and underlie fictive eupnea, whereas only one burst mechanism seems to be critical for gasping generation in vitro.