DEVELOPMENTAL-CHANGES IN THE HYPOXIC RESPONSE OF THE HYPOGLOSSUS RESPIRATORY MOTOR OUTPUT IN-VITRO

The transverse brain stem slice of mice containing the pre-Botzinger c omplex (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 preparat ion generates, at different postnatal stages [postnatal day (P)0-22], spontaneous rhythmic activity in hypoglossal (XII) rootlets that are k nown to occur in synchrony with periodic bursts of neurons in the PBC. It is assumed that this rhythmic activity reflects respiratory rhythm ic 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 neo nates (P0-7), anoxia did not significantly affect the amplitude of int egrated XII bursts. Secondary depression never led to a cessation of r hythmic activity. In mice older than P7, augmentation was accompanied by a significant increase in the amplitude of XII bursts. A significan t decrease of the amplitude of XII bursts occurred during secondary de pression. This depression led always to cessation of rhythmic activity in XII rootlets. The anoxia-induced response of the respiratory rhyth mic XII motor output is biphasic and changes during development in a s imilar way to the in vivo respiratory network. Whether this biphasic r esponse is due to a biphasic response of the respiratory rhythm genera tor and/or to a biphasic modulation of the XII motor nucleus remains u nresolved and needs further cellular analysis. We propose that the tra nsverse slice is a useful model system for examination of the mechanis ms underlying the hypoxic response.