The distribution of thirteen GABAA receptor subunit mRNAs in the rat brain. III. Embryonic and postnatal development.
The embryonic and postnatal expression of 13 GABAA receptor subunit genes in the rat CNS was studied by in situ hybridization. Each transcript exhibited a unique regional and temporal developmental expression profile. For example, in both embryonic and early postnatal cortex and thalamus, expression of the alpha 2, alpha 3, alpha 5, and beta 3 mRNAs was pronounced. In particular, the alpha 5 gene expression underwent a prominent peak in early brain. Subsequently, the thalamocortical expression of these four genes substantially diminished and was superseded in the adult by the alpha 1, alpha 4, beta 2, and delta subunit mRNAs. Similarly, gamma 1 and gamma 3 gene expression also dropped markedly during development, their initial stronger expression being restricted to relatively few structures. In contrast, gamma 2 gene expression was widespread and mostly remained constant with increasing age. The medial septum and globus pallidus were regions expressing few subunits in both early postnatal and adult stages, allowing clear developmental combinatorial changes to be inferred (alpha 2/alpha 3 beta 2 gamma 2 to alpha 1 beta 2 gamma 2, alpha 2/alpha 3 beta 2 gamma 1 to alpha 1 beta 2 gamma 1/gamma 2, respectively). In contrast, cerebellar Purkinje cells exhibited no developmental switch, expressing only the alpha 1, beta 2, beta 3, and gamma 2 mRNAs from birth to adult. Certain GABAA transcripts were also detected in germinal zones (e.g., beta 1, beta 3, gamma 1) and in embryonic peripheral tissues such as dorsal root ganglia (e.g., alpha 2, alpha 3, beta 3, gamma 2) and intestine (gamma 3). Some parallels in regional and temporal CNS expression were noted (e.g., alpha 1 beta 2, alpha 2 beta 3, alpha 4/alpha 6 delta), whereas the alpha 5 and beta 1 regional mRNA expressions converted over time. The changes of GABAA receptor subunit gene expression suggest a molecular explanation for earlier observations on changing ligand binding affinities. Thus, the composition, and presumably properties, of embryonic/early postnatal rat GABAA receptors differs markedly from those expressed in the adult brain.