Developmental changes in the hypoxic response of the hypoglossus respiratory motor output in vitro

The transverse brain stem slice of mice containing the pre-Bötzinger complex (PBC), a region essential for respiratory rhythm generation in vitro, was used to study developmental changes of the response of the in vitro respiratory network to severe hypoxia (anoxia). This preparation generates, at different postnatal stages [postnatal day (P)0-22], spontaneous rhythmic activity in hypoglossal (XII) rootlets that are known to occur in synchrony with periodic bursts of neurons in the PBC. It is assumed that this rhythmic activity reflects respiratory rhythmic activity. At all examined stages anoxia led to a biphasic response: the frequency of rhythmic XII activity initially increased ("primary augmentation") and then decreased ("secondary depression"). In neonates (P0-7), anoxia did not significantly affect the amplitude of integrated XII bursts. Secondary depression never led to a cessation of rhythmic activity. In mice older than P7, augmentation was accompanied by a significant increase in the amplitude of XII bursts. A significant decrease of the amplitude of XII bursts occurred during secondary depression. This depression led always to cessation of rhythmic activity in XII rootlets. The anoxia-induced response of the respiratory rhythmic XII motor output is biphasic and changes during development in a similar way to the in vivo respiratory network. Whether this biphasic response is due to a biphasic response of the respiratory rhythm generator and/or to a biphasic modulation of the XII motor nucleus remains unresolved and needs further cellular analysis. We propose that the transverse slice is a useful model system for examination of the mechanisms underlying the hypoxic response.