GABA, GAD, AND GABA(A) RECEPTOR ALPHA-4, BETA-1, AND GAMMA-1 SUBUNITSARE EXPRESSED IN THE LATE EMBRYONIC AND EARLY POSTNATAL NEOCORTICAL GERMINAL MATRIX AND COINCIDE WITH GLIOGENESIS

Increasing evidence indicates that the classical, fast-acting neurotra nsmitter gamma-amino butyric acid (GABA) may initially act as morphoge n in cell proliferation and differentiation via specific receptors. In view of the potential roles for GABA in central nervous system develo pment, we examined the expression of GABA, GABA(A) receptor beta(1) an d gamma(1) subunits by immunocytochemistry and the expression of trans cripts for two GABA-synthesizing enzymes, glutamate decarboxylase (GAD (65), GAD(67) mRNAs), and for alpha 4, beta 1, and gamma 1 subunits of GABA(A) receptor by in situ hybridization in the developing neocortex . Tissue sections were taken from embryonic days (E) 17 and E20 embryo s and newborn rats (PO). The embryos' mothers and newborn rats had bee n injected with 5-bromo-2'-deoxyuridine (BrdU) and had survived for 2 hours. At E17, BrdU-positive cells were largely restricted in the synt hetic zone at the ventricular margin when cortical neurogenesis was st ill active. GAD mRNAs and GABA immunoreactivity were detected in the s ubventricular zone, while alpha 4, beta(1), and gamma(1) subunits were abundant in the ventricular zone. At E20 and PO, when neurogenesis ha d largely ceased and gliogenesis had commenced, BrdU-positive cells we re found throughout the ventricular zone with GABA, GAD mRNAs, and alp ha 4, beta(1), and gamma(1) subunits. GABA, GAD mRNAs and alpha 4, bet a 1, and gamma 1 subunit signals intensified in the ventricular zone f rom E17 to PO as gliogenesis preceded. Thus, specific components of a putative GABAergic circuit are expressed in cells of the ventricular z one during the late embryonic/early postnatal period coincident with g liogenesis, suggesting a role for GABA in glial cell proliferation. (C ) 1998 Wiley-Liss, Inc.