Area and lamina-specific expression of GABA<SUB>A</SUB> receptor subunit mRNAs in monkey cerebral cortex

Abstract

Seven monkey-specific cDNAs corresponding to alpha 1, alpha 2, alpha 4, alpha 5, beta 1, beta 2, and gamma 2 GABAA receptor subunits were isolated and cloned; radioactive cDNA and cRNA probes were used for Northern blot analysis and in situ hybridization histochemistry of the primary visual, somatosensory, motor, temporal, and anterior parietal areas. alpha 1, beta 2, and gamma 2 subunit mRNAs were expressed at much higher levels than the other mRNAs, indicating that most cortical GABAA receptors are assembled from these three subunits. alpha 1, beta 2, and gamma 2 were also more highly expressed in area 17 than in all other areas, reflecting the greater density of GABA cells and synapses in area 17. In all cortical areas, each subunit mRNA showed an individual pattern of laminar expression. alpha 1, beta 2, and gamma 2 subunit mRNAs were particularly high in layers II-III, IV, and VI, tending to follow patterns of receptor binding and immunocytochemical staining. The other transcripts had different patterns, which did not match binding or immunocytochemical localization patterns. alpha 5 subunit mRNAs, which are highly expressed in development, were enriched in layer VI and the underlying white matter of visual cortex and in a layer IV-like strip in area 4, possibly reflecting the involvement of receptors formed from alpha 5 polypeptides in trophic interactions in the cortical subplate and in the transient layer IV during development of these areas. Monocular deprivation for 1-3 weeks, induced by intravitreal injection of tetrodotoxin, resulted in substantial reductions in levels of alpha 1, beta 2, and gamma 2 subunit mRNAs in deprived ocular dominance columns of the visual cortex, but the other subunit mRNAs were largely unaffected by monocular deprivation. In cortical layers in which expression of any of the transcripts was high, all neurons appeared to express the gene, but in layers in which expression was low or moderate, differences in the degree of labeling of individual neurons suggested that some neurons may not express certain subunit transcripts in detectable amounts. Laminar differences in expression of different GABAA receptor subunits in cerebral cortex suggest the assembly of functional receptors from different arrangements of available subunits in different types of cell. Receptors with different functional properties may be assembled from different combinations of subunit polypeptides in different layers and in the visual cortex may be differentially regulated under activity-dependent conditions.