Initial development of gamma-aminobutyric acid immunoreactivity in the human cerebral cortex.

The development of cortical cells immunoreactive for gamma-aminobutyric acid (GABA) was studied in human cerebral cortex in the first trimester of gestation (from 4 to 13 gestational weeks; g.w.). The first GABA-immunoreactive (IR) cells were observed at 6.5 g.w., i.e., before the appearance of the cortical plate, which gives rise to a majority of the adult cortical layers. GABA-IR cells were found initially in the telencephalic wall, where a lateromedial gradient in the density of GABA-positive cells was observed at this early developmental time point, but not at later stages. At 7 g.w., as the cortical plate emerged in the ventrolateral region of the cerebral vesicle, GABA-immunoreactive cells were found dorsal and ventral to the developing cortical plate. At this stage, immunoreactivity was also observed in the other transient developmental zones of the cortical anlage: in the subplate layer and in the intermediate, subventricular and ventricular zones. From 8 to 9 g.w. and continuing throughout the end of the studied period (13 g.w.), GABA-IR cells were distributed throughout the full width of the telencephalic wall, and, at 13 g.w., the newly formed subpial granular layer contained GABA-immunoreactive cells, as well. However, the predominant sites for GABA immunoreactivity remained the prospective layer I and the subplate. The population of GABA-positive cells described here was not immunoreactive for glial fibrillary acidic protein (GFAP) at any gestational age examined and, therefore, probably represents GABA-containing neurons. The observation that GABA-IR neurons appear in human developing cortex slightly before the cortical plate formation and beginning of synaptogenesis (6.5 g.w.) suggests that GABA plays an important role in the initial organization of the developing human cerebral cortex.