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

Abstract

Involvement of chloride-dependent, gamma-aminobutyric acid-(GABA-) like synaptic inhibition in the generation of respiratory rhythm was studied in brainstem-spinal 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 microM) 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 microM bicuculline, 10 microM picrotoxin, 5 microM 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 microM 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.(ABSTRACT TRUNCATED AT 250 WORDS)