Co-existent expression of GABA A receptorβ 2, β 3 andγ 2 subunit messenger RNAs during embryogenesis and early postnatal development of the rat central nervous system

Abstract

The expression ofβ 1,β 2,β 3,γ 2 and δ subunit messenger RNAs of the GABA A receptor was followed by in situ hybridization histochemistry using radiolabeled oligodeoxynucleotide probes in sections of embryonic (E12–21) and early postnatal (P1–5) rat. β2,β 3 andγ 2 subunit messenger RNAs were first detectable at E15 in the spinal cord (ventral > dorsal) and lower central nervous system regions (e.g. pons, medulla and thalamus).β 3 subunit messenger RNA was abundantly expressed in olfactory bulb neurons at E15. At E17, the expression pattern of these subunit messenger RNAs continued in the lower central nervous system. In the upper central nervous system,β 2,β 3 andγ 2 subunit messenger RNAs were first detectable in the outer layer of the hippocampal and entire cortical neuroepithelium. The expression for bothβ 3 andγ 2 subunit messenger RNAs increased significantly over that observed at E15, whereasβ 2 subunit messenger RNA increased to a lesser extent and was more discretely expressed in inferior colliculus, cerebellar neuroepithelium and spinal cord (ventral = dorsal). By E19, messenger RNAs forβ 2,β 3 andγ 2 subunits displayed a widespread and abundant co-existent distribution throughout the central nervous system. Exceptions to this co-expression were the absence ofβ 2 messenger RNA in the dentate gyrus andβ 3 messenger RNA in entorhinal cortex, areas in which they are present in adult. There was also a differential distribution of subunit messenger RNAs in developing olfactory bulb at E19–20: the glomerular cells preferentially expressedβ 3 andγ 2 subunit messenger RNAs; the mitral cells preferentially expressedβ 2 subunit messenger RNA; inner granule cells expressed moderate levels ofβ 2,β 3 andγ 2 subunit messenger RNAs. Expression ofβ 2,β 3 andγ 2 messenger RNAs was also anatomically co-existent at P5. In addition, significant expression ofβ 1 and δ subunit messenger RNAs was apparent in hippocampus and entorhinal cortex. The identity of theγ 2 expressed between E15 and E21 was shown to be mostly the short isoform ofγ 2 subunit messenger RNA. Expression of both forms was evident beginning around P3–5. These results indicate that during the late embryonic and early postnatal period of development,β 2,β 3 andγ 2 subunit messenger RNAs are abundantly expressed and co-localized to most central nervous system regions. The anatomical and cellular distribution of these GABA A subunit messenger RNAs, as well as those coding for specific α subunits [Poulter M.O. et al. (1992) J. Neurosci. 12, 2888–2890] indicates that the expression of GABA A receptor subunit messenger RNA is a complex and dynamic process, giving rise to a pattern that has constant and variable features which often differ from distributions seen in the adult CNS. This ontogenetic profile is consistent with the evidence that GABA A receptors play a role in synaptogenesis and/or cellular differentiation.