Laminar distribution of GABA sub(A) receptor alpha sub(1), beta sub(2), and gamma sub(2) subunit mRNAs in the granular and agranular frontal cortex of the rat during pre- and postnatal development

The expression of mRNAs encoding the three GABA sub(A) receptor subunits that are associated with the most abundant benzodiazepine-sensitive GABA sub(A) receptor in adult cortex, that is, the alpha sub(1), beta sub(2), and gamma sub(2) subunits, was studied in rat cortex during pre- and postnatal development by means of in situ hybridization. gamma sub(2) and beta sub(2) mRNAs become detectable in neocortex at gestational day 16 (GD16), alpha sub(1) at GD18. gamma sub(2) mRNA exhibits the highest level of expression at early ages, while alpha sub(1) mRNA levels are low. beta sub(2) mRNA rises steeply during the last days of gestation. Around birth, it shows the highest expression of the three subunits studied in cortex, and increases further until postnatal day 15 (PD15). The expression of alpha sub(1) subunit mRNA also increases markedly shortly before birth and accelerates between PD8 and PD15, when it reaches higher levels than the other two subunits. Following the initial high expression, gamma sub(2) mRNA increases gradually and slowly until PD25. During prenatal development, highest expression of all three subunit mRNAs is found in the upper layers of cortex, that is, cortical plate and marginal zone. The subplate layer does not start to express GABA sub(A) receptor subunit mRNAs until GD18. At birth, all developing layers of the cortex express mRNAs for the three subunits, except the marginal zone. Highest levels are found in the upper part of the cortical plate. At the end of the first postnatal week (PD8), the laminar distribution of mRNA expression in neocortex becomes more differentiated. For all three subunit mRNAs, highest expression is then observed in neuron-like cells in layer IV in the granular areas, and over layers III and upper V in agranular areas. Subsequently, between PD8 and PD25, increasing levels of expression are observed over the pyramidal cell layer V. This regionally differentiated, developmental pattern suggests a close relationship between development of GABA sub(A) receptor subunits, ingrowth of thalamocortical projections, and maturation of neocortical circuitry.