Is GABA excitatory or inhibitory in the developing brain?

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In the superior colliculus (SC) of the fetal rat brain, changes in intracellular Cl^- following focal stimulation of the SC were examined by in vivo optical recordings with Cl^- sensitive fluorescent dye. In addition, the effect of hypoxia on changes in intracellular Cl^- induced by focal SC stimulation was also examined in fetal rats which were connected with the dams by the umbilical cord. Pregnant rats were anesthetized with urethane (1.3g/kg, i.p.), the uterus was exposed by cesarean section, and partially cut to exposure of the fetus. The fetal head was attached to a stereotaxic apparatus with dental cement, and the surface of the SC was exposed. Stimulating electrodes were implanted in the rostral part of the SC.Cl^- sensitive dye was applied to the surface of the SC for optical recording of intracellular Cl^-. Fetal asphyxia was brought about by occluding the umbilical cord with a fine clip, while the recovery of the umbilical blood flow was attained by local application of papa … More verine, a relaxant of blood vessels, to the occlusion site.Focal SC stimulation increased intracellular Cl^-. This response was found to extend caudally to the entire SC from the stimulating site. In a total of 25 fetuses examined, 16 revealed Cl^- influx, 1 Cl^- efflux, and 2 both Cl^- influx and efflux following focal SC stimulation. The remaining 6 showed no change in intracellular Cl^-. Furthermore, a total of 12 fetuses were examined to assess the effect on the SC stimulation induced changes in intracellular Cl^- of hypoxia induced by umbilical cord occlusion. Before umbilical cord occlusion, 8 fetuses showed Cl^- influx following focal SC stimulation. However, 3 hours after the occlusion, the number of fetuses showing Cl^- influx was only one, and 10 fetuses revealed both Cl^- influx and efflux. The changes in intracellular Cl^- were attenuated by application of the GABA antagonist bicuculline in all cases (n=5) before umbilical cord occlusion and in 2 of 8 cases after the occlusion. These results suggest that following hypoxia Cl^- influx induced by focal SC stimulation is converted to Cl^- efflux. In addition, the changes in intracellular Cl^- are thought to occur via GABA receptors. Less