Postnatal changes in the mammalian respiratory network as revealed by the transverse brainstem slice of mice

Abstract

1. Spontaneous rhythmic activity in hypoglossal (XII) rootlets is generated at all postnatal stages from postnatal day (P) 0 to P22 in the transverse brainstem slice of mice containing the pre-Botzinger complex (PBC). The PBC is known to be a region essential for respiratory rhythm generation. It contains neurones generating periodic bursts that occur in synchrony with rhythmic XII activity. This synchrony indicates that the rhythmic PBC activity generated by the transverse slice is the central respiratory rhythm. 2. The strength of coupling between XII bursts and PBC bursts decreased during early postnatal development. In younger mice (P0-4) each burst in XII rootlets corresponded to one burst in the PBC. In older mice (P5-18) one burst in XII rootlets occurred only every third to fourth burst in PBC neurones. 3. Cycle length and burst duration of rhythmic XII activity did not change significantly during the first three postnatal weeks. However, the pattern of XII bursts changed from decrementing (P0-7) to bell shaped (P8-18) while the rate of rise of XII bursts decreased significantly. 4. The rate of rise of rhythmic depolarizations in neurones of the PBC discharging in phase with XII bursts ('inspiratory neurones') decreased with postnatal development. During interburst intervals, membrane potentials of neurones of older mice (P6-18) were characterized by waves of synaptic input that were not observed in neonatal animals (P0-5). 5. Blockade of glycine receptors by strychnine increased the frequency of rhythmic XII activity in neonatal and older mice (P0-22). Although in expiratory PBC neurones glycinergic transmission was blocked at 10 μM strychnine, in inspiratory PBC neurones and XII rootlets even higher concentrations of up to 50 μM strychnine failed to abolish rhythmic activity.