Jones E G
Department of Anatomy and Neurobiology, University of California, Irvine 92717, USA.
Can J Physiol Pharmacol. 1997 May;75(5):452-69.
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.
分离并克隆了与α1、α2、α4、α5、β1、β2和γ2 GABAA受体亚基对应的七个猴特异性cDNA；放射性cDNA和cRNA探针用于初级视觉、体感、运动、颞叶和顶叶前部区域的Northern印迹分析和原位杂交组织化学。α1、β2和γ2亚基mRNA的表达水平远高于其他mRNA，表明大多数皮质GABAA受体由这三个亚基组装而成。α1、β2和γ2在17区的表达也高于所有其他区域，反映出17区GABA细胞和突触的密度更高。在所有皮质区域，每个亚基mRNA都呈现出独特的层状表达模式。α1、β2和γ2亚基mRNA在II-III层、IV层和VI层特别高，倾向于遵循受体结合和免疫细胞化学染色模式。其他转录本具有不同的模式，与结合或免疫细胞化学定位模式不匹配。在发育过程中高度表达的α5亚基mRNA在视觉皮层的VI层和下层白质以及4区类似IV层的条带中富集，这可能反映了由α5多肽形成的受体在这些区域发育过程中皮质下板和短暂的IV层的营养相互作用中的参与。通过玻璃体内注射河豚毒素诱导的1-3周单眼剥夺导致视觉皮层剥夺眼优势柱中α1、β2和γ2亚基mRNA水平大幅降低，但其他亚基mRNA在很大程度上不受单眼剥夺的影响。在任何转录本表达高的皮质层中，所有神经元似乎都表达该基因，但在表达低或中等的层中，单个神经元标记程度的差异表明一些神经元可能不以可检测的量表达某些亚基转录本。大脑皮层中不同GABAA受体亚基表达的层状差异表明，功能性受体是由不同类型细胞中可用亚基的不同排列组装而成。具有不同功能特性的受体可能由不同层中亚基多肽的不同组合组装而成，并且在视觉皮层中可能在活动依赖条件下受到不同的调节。
