Fig. 3: Mafa-4A-induced breath holding apneas rely on GABAergic synaptic transmission.
From: Mafa-dependent GABAergic activity promotes mouse neonatal apneas
a The GABAA-receptor antagonist PTZ increases regular breathing rates in control (gray symbols, n = 10, two-sided paired Student’s t test, P < 0.0001, df = 9, t = 6.851) and Mafan4A/n4A (red symbols, n = 10, two-sided paired Student’s t test P = 0.040, df = 9, t = 2.393) at P0 + 12 h (Student’s t test). b PTZ has no effect on the apneic time fraction of control pups (n = 10, gray symbols, two-sided Wilcoxon paired test, P = 0.921) but PTZ and not NaCl reduces the apneic time fraction of Mafan4A/n4A mutant pups (n = 10, red symbols, two-way ANOVA F(1,18) = 8.176, P = 0.0104 followed by Bonferroni’s multiple comparison test, P = 0.0202 for PTZ; P = 0.5147 for NaCl). c PTZ reduces breath holding apneas in control (n = 10 pups, two-sided Wilcoxon test P = 0.0039) and Mafan4A/n4A mutant pups (n = 10, two-sided paired Student’s t test P = 0,0098, df = 9, t = 3.264) but not central-like apneas of control (two-sided Wilcoxon test P = 0.0645) nor of Mafan4A/n4A mutant pups (paired Student’s t-test P = 0.2791, df = 9, t = 1.152). d Genetic recombination to target the 4A mutation in inhibitory neurons. e Plethysmographic recordings of control (upper trace) and of VGATMafa4A mutant pups (lower trace) at P0 + 12 h showing apneic breathing and upwards pressure shifts (arrows) terminating breath holding apneas. f Poincaré plots of a control (left, black symbols) and of a MafaVGAT4A mutant presenting with increased number of apneas (red symbols beyond the CORC). g The apneic time fraction of MafaVGAT4A pups (n = 10) is about double that of control littermates (n = 13, two-sided unpaired t-test P = 0.0263, df = 22, t = 2.382). h The apneic time fraction corresponding to breath holding apnea is three-fold higher in MafaVGAT4A (VGATCre/+, n = 10, red symbols) than controls (VGAT+/+, n = 13, gray symbols, two-sided Mann–Whitney test P = 0.002, U = 10) while that corresponding to central-like apneas is not changed by the mutation (unpaired t-test P = 0.5774, df = 20, t = 0.5663). Plots represent mean ± sem.
