GABA, GAD, and GABA(A) receptor alpha4, beta1, and gamma1 subunits are expressed in the late embryonic and early postnatal neocortical germinal matrix and coincide with gliogenesis.

Abstract

Increasing evidence indicates that the classical, fast-acting neurotransmitter gamma-amino butyric acid (GABA) may initially act as morphogen in cell proliferation and differentiation via specific receptors. In view of the potential roles for GABA in central nervous system development, we examined the expression of GABA, GABA(A) receptor beta1 and gamma1 subunits by immunocytochemistry and the expression of transcripts for two GABA-synthesizing enzymes, glutamate decarboxylase (GAD65, GAD67 mRNAs), and for alpha4, beta1, and gamma1 subunits of GABA(A) receptor by in situ hybridization in the developing neocortex. Tissue sections were taken from embryonic days (E) 17 and E20 embryos and newborn rats (P0). The embryos' mothers and newborn rats had been injected with 5-bromo-2'-deoxyuridine (BrdU) and had survived for 2 hours. At E17, BrdU-positive cells were largely restricted in the synthetic zone at the ventricular margin when cortical neurogenesis was still active. GAD mRNAs and GABA immunoreactivity were detected in the subventricular zone, while alpha4, beta1, and gamma1 subunits were abundant in the ventricular zone. At E20 and P0, when neurogenesis had largely ceased and gliogenesis had commenced, BrdU-positive cells were found throughout the ventricular zone with GABA, GAD mRNAs, and alpha4, beta1, and gamma1 subunits. GABA, GAD mRNAs and alpha4, beta1, and gamma1 subunit signals intensified in the ventricular zone from E17 to P0 as gliogenesis proceeded. Thus, specific components of a putative GABAergic circuit are expressed in cells of the ventricular zone during the late embryonic/early postnatal period coincident with gliogenesis, suggesting a role for GABA in glial cell proliferation.