Differential ontogeny of GABABreceptor‐mediated pre‐ and postsynaptic modulation of GABA and glycine transmission in respiratory rhythm‐generating network in mouse

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Abstract
Rhythm generation in mature respiratory networks is influenced strongly by synaptic inhibition. In early neonates, GABAA‐receptor‐ and glycine‐receptor‐mediated inhibition is not present, thus the question arises as to whether GABAB‐receptor‐mediated inhibition plays an important role. Using brainstem slices of neonatal mice (postnatal day, P0‐P15), we analysed the role of GABAB‐mediated modulation of GABA and glycine synaptic transmission in the respiratory network. Blockade of GABA uptake by nipecotic acid (0.25–2 mm) reduced the respiratory frequency. This reduction was prevented by the selective GABAB receptor antagonist CGP55845A (CGP) alone at P0‐P3, but by bicuculline as well as CGP at P7‐P15. Blockade of GABAB receptors by CGP increased the respiratory frequency at P0‐P3, whereas it caused a reduction of frequency in older animals. The effect of CGP on respiratory frequency was diminished in the presence of bicuculline and strychnine in older but not in younger animals. The relative contribution of GABAB‐receptor‐mediated pre‐ and postsynaptic modulation was examined by analysing the effect of GABAB receptors on spontaneous and miniature IPSCs. In younger animals (P0‐P3), the GABAB receptor agonist baclofen had no detectable effect on IPSC frequency, but caused a significant decrease in the amplitude. In older animals (P7‐P15), baclofen decreased both the frequency and amplitude of spontaneous and miniature IPSCs. These results demonstrate that GABAB‐receptor‐mediated postsynaptic modulation plays an important role in the respiratory network from P0 on. GABAB‐receptor‐mediated presynaptic modulation develops with a longer postnatal latency, and becomes predominant within the first postnatal week.