Prenatal development of the intrinsic neurons of the rat neocortex: A comparative study of the distribution of GABA-immunoreactive cells and the GABA A receptor

Abstract

The ontogenesis of cells showing GABA-like immunoreactivity, and the distribution of the immunoreactivity for the GABA A receptor were studied immunocytochemically in the prenatal rat brain. By embryonic day 14, a few GABA-like immunoreactive (GABA-positive) cells scattered at the subpial limit of the marginal zone (primordial plexiform layer) in the lateral part of the developing cortex. GABA-positive cells appeared progressively within the dorsal and medial sectors of the primordial plexiform layer, occupying deeper positions within the layer. The immunoreactivity for the GABA A receptor covered the whole thickness of the primordial plexiform layer. By embryonic day 16, most GABA-positive cells populated three distinct laminar compartments of the developing cortex: the prospective lamina I, the subplate, and the lower part of the intermediate zone. The GABA-positive cells of the lower intermediate zone appeared to be typical of the developing cerebral cortex of the rat; their neuronal nature was assessed immunocytochemically, using monoclonal antibodies against microtubuleassociated protein 2, mainly expressed in neuronal somata and dendrites, and against intermediate filament protein vimentin, expressed in glia. The lower intermediate zone contained cells immunoreactive for microtubule-associated protein 2, although the immunostaining was less intense than in the prospective lamina I and the subplate. Preliminary results showed no vimentin-positive cells in the lower intermediate zone. At embryonic day 16, immunoreactivity for the GABA A receptor was present within the prospective lamina I and the subplate, but not in the lower intermediate zone. From embryonic day 18 onwards, the immunostaining for the GABA A receptor labelled, unambiguously, the subplate as a lamina clearly separated from the suprajacent cortical plate. At embryonic day 18, the GABA A receptor started to be expressed within the lower, differentiating part of the cortical plate. Within the cortical plate, the expression of GABA in neural cell perikarya, and the immunostaining for the GABA A receptor, followed a similar spatio-temporal (“inside-out”) gradient during pre- and early postnatal stages. Most GABA-positive cells of the lower intermediate zone started to disappear (or stopped the expression of GABA) by embryonic day 20, but some remained until adulthood. A similar time-course was observed for the microtubule-associated protein 2-immunoreactive cell population located at the same level. It is hypothesized here that, in the cerebral cortex of the rat, the GABA-like immunoreactive cells of the lower intermediate zone may contribute to the population of interstitial cells of the adult white matter, while the subplate remains in the adult as layer VIb.