Differential and transient expression of GABAA receptor alpha-subunit mRNAs in the developing rat CNS

Abstract

The expression of mRNAs coding for alpha 1, alpha 2, alpha 3, alpha 5, and alpha 6 subunits of the GABAA neurotransmitter receptor was followed during the development of the rat CNS by in situ hybridization histochemistry. Expression of these subunit mRNAs in tissue sections of embryonic day 15 and 17 (E15, E17) whole rat and in brain at ages greater than E17 to adult were varied, transient, and region specific. Subunit mRNAs first detected at E15 were those coding for the alpha 2 and alpha 3 subunits. At E17, alpha 2, alpha 3, and alpha 5 mRNAs were present in abundance in numerous areas in the CNS, with lower but significant amounts of alpha 6 being present in the cortical neuroepithelial layers. However, alpha 6 subunit mRNA expression in the cortex declined until little or no alpha 6 mRNA was detected at E19. alpha 1 subunit mRNA first appeared at E19 in the cortex, followed by expression in the hippocampus by postnatal 5 (PN5). Particularly high expression of alpha 2 and alpha 5 subunit mRNAs was detected throughout the developing CNS, but they were most abundant in the olfactory bulb neurons. The high levels of alpha 2 and alpha 5 subunit mRNAs began to decline around PN5 to the amounts observed in adult. These results demonstrate that numerous GABAA receptor alpha-subunits are expressed before birth in a region- and age-specific manner. This complex and varied expression supports the hypothesis that GABA may play a role in cellular and synaptic differentiation.

Ionotropic GABA receptor expression in the lung during development

“…2A) were relatively high in mid-gestation, but decreased in late gestation and remained low in adult. Interestingly, some of those subunits, such as α2 and α5, were also less abundant in the adult brain than in the fetal brain (Poulter et al, 1992). Some subunits in the lung from Groups 2, 3 and 4 were constitutively expressed or only slightly fluctuated from mid-gestation to adult (Fig.…”

“…This demonstrates that these subunits are ontogeny-"conserved" in the lung. Many of these subunits, including α3, α4, β2, and γ2, were also more developmentally "conserved" than other subunits in the brain (Huang and Dillon, 2002;Poulter et al, 1992). These subunits may be the basic components for forming functional GABA receptors in both embryonic and postnatal brains and lungs.…”

The expression of GABAAreceptors during the development of the rabbit retina

“…However, an association between the appearance of the GABA A receptors and synaptogenesis and/or cellular differentiation has been suggested (Poulter et al 1993). The beta subunits are usually present throughout development, whereas the alpha subunits change, perhaps regulating the formation of synapses or other differentiation events (Poulter et al 1992(Poulter et al , 1993). This general scheme may then also be applicable to the retina, because as shown here, the beta 2/3 subunits appear before the alpha 1 .…”

GABAAReceptor Subunit Composition and Functional Properties of Cl−Channels with Differential Sensitivity to Zolpidem in Embryonic Rat Hippocampal Cells

“…During embryonic development, GABA A receptor subunits emerge throughout the rat C NS, with elevated expressions of ␣2, ␣3, ␣4, and ␣5 subunit transcripts but quite low levels of the ␣1 subunit mRNA (Laurie et al, 1992;Poulter et al, 1992). The emergence of the ␣1-containing GABA A receptors during the early postnatal period parallels the appearance of fast inhibitory GABAergic transients in hippocampal and cortical regions, whereas the abundance of other ␣ subunits before birth is presumed to be involved in morphogenic events.…”