Inhibitory synaptic inputs to the respiratory rhythm generator in the medulla isolated from newborn rats

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Abstract
Involvement of chloride-dependent, gamma-aminobutyric acid-(GABA-) like synaptic inhibition in the generation of respiratory rhythm was studied in brainstemspinal cord preparations isolated from newborn rats. Primary respiratory rhythm is presumably generated within the rostral ventrolateral medulla, the site of Pre-I neurones, the firing of which precedes inspiration. Therefore, we examined the responses of Pre-I and inspiratory neurones to GABA antagonists (picrotoxin and bicuculline), a glycine antagonist (strychnine) and reduced chloride concentration in the perfusate. These antagonists (2–20 μM) and reduction of chloride concentration reversibly blocked the transient inhibition of Pre-I activity that occurred during the inspiratory phase. The rhythmic Pre-I and inspiratory neurone activity remained. Changes in the firing properties of Pre-I and inspiratory neurones in 10 μM bicuculline, 10 μM picrotoxin, 5 μM strychnine or reduction of chloride concentration to 40% of normal were analysed statistically. Burst rate of Pre-I neurones tended to increase during these treatments. Delay time from initiation of Pre-I firing to the peak of C4 motorneurone inspiratory activity tended to decrease except during reduced chloride concentration. Changes in mean intraburst firing frequency of Pre-I neurones were not consistent; increase (32%), no change (38%) or decrease (30%). Burst duration of inspiratory neurones decreased. Intraburst firing frequency of inspiratory neurones tended to increase except in 5 μM strychnine. GABA (0.1 mM) or glycine (0.2 mM) reduced the intraburst firing frequency and burst rate of Pre-I neurones, but did not affect the intraburst firing frequency of inspiratory neurones. The burst duration of inspiratory neurones increased during GABA and glycine treatment. The results suggest: 1. Inhibition of Pre-I activity during the inspiratory phase depends on chloride-dependent, GABA- (or glycine-) like inhibitory synaptic interaction (probably inhibitory synaptic inputs to Pre-I neurones), but Pre-I rhythm generation does not require this phasic inhibition. 2. Tonic GABAA-like inhibition (where A denotes the receptor sub-type) might be involved in the modulation of rhythm generation and inspiratory pattern generation.