THE HYPOXIC RESPONSE OF NEURONS WITHIN THE IN-VITRO MAMMALIAN RESPIRATORY NETWORK

1. The transverse brainstem slice preparation containing the pre-Botzi nger complex (PBC) was used in mice to study developmental changes of the response of the in vitro respiratory network to hypoxia. This prep aration generates at different postnatal stages (postnatal days (P) 0- 22) spontaneous rhythmic activity in hypoglossal (XII) rootlets that o ccur in synchrony with periodic bursts of neurones in the PBC. 2. In s lices from P0-4 mice, hypoxia did not significantly affect the amplitu de of rhythmic synaptic drive potentials in four of five inspiratory n eurones. Hypoxia reduced, but did not suppress, the amplitude of synap tic drive potentials in only one inspiratory neurone. Spike discharge and phasic 'inspiratory' hyperpolarizations of sh expiratory neurones were suppressed during hypoxia revealing a phasic 'inspiratory' depola rization. 3. The coupling between rhythmic activity in PBC neurones an d XII bursts occurred under control conditions in preparations from P0 -4 mice in a 1:1 manner (n = 11) and from mice older than P5 in a 3:1 manner (n = 9). During hypoxia, PBC and XII activity were linked in a 1:1 manner in all slices. 4. In six of fourteen inspiratory PBC neuron es, the amplitude of synaptic drive potentials of slices from mice old er than P8 was increased during the period of augmentation, reduced du ring the Period of depression and suppressed during a hypoxic response which we refer to as central apnoea. Augmentation led to a weak-to-mo derate membrane depolarization which on average was 4.8+/-3.7 mV. This depolarization was followed by a hyperpolarization of 6.2+/-4.1 mV on ly in four inspiratory neurones. In the majority of neurones (n = 9), however, membrane depolarization remained stable and was not followed by hyperpolarization. In expiratory neurones (n = 12) from this age gr oup hypoxia suppressed phasic hyperpolarizations that occurred in sync hrony with XII bursts. As similarly seen in inspiratory neurones, memb rane potentials were depolarized by 5.1+/-4.1 mV during the period of hypoxic augmentation. 5. The hypoxic response of respiratory neurones within the pre-Botzinger complex resembles the response of neurones th at were previously described under in vivo conditions. Thus we conclud e that the 'transverse rhythmic slice' is a good model for studying th e hypoxic response of the respiratory network under in vitro condition s.