Gao B, Fritschy J M
Institute of Pharmacology, University of Zürich, Switzerland.
Eur J Neurosci. 1994 May 1;6(5):837-53. doi: 10.1111/j.1460-9568.1994.tb00994.x.
The identification of a large variety of GABAA receptor subunits by molecular cloning suggests the existence of multiple receptor subtypes differing in localization and functional properties. In the present study we analysed immunohistochemically the cellular distribution of GABAA receptors containing the alpha 1 subunit in the rat hippocampus with a subunit-specific antiserum. Prominent staining of numerous interneurons was evident in Ammon's horn and the dentate gyrus, which contrasted with moderate and diffuse immunoreactivity in the dendritic layers of pyramidal and granule cells. Double immunofluorescence staining with antibodies to GABA revealed that a subset of GABAergic neurons in the hippocampus were immunoreactive for the alpha 1 subunit. To determine whether these cells represent distinct subpopulations of interneurons, we analysed the co-localization of the GABAA receptor alpha 1 subunit with selective markers of hippocampal interneurons (selected calcium-binding proteins and neuropeptides). In both Ammon's horn and the dentate gyrus, all parvalbumin-positive neurons and 50% of calretinin-positive neurons were double-labelled, whereas interneurons containing calbindin-D28k were devoid of alpha 1 subunit staining. Similarly, most neurons positive for neuropeptide Y and a subset of somatostatin-positive cells were double-labelled, in contrast to cholecystokinin- and vasoactive intestinal peptide-containing cells, which lacked the alpha 1 subunit staining. These results demonstrate cell-specific expression of GABAA receptors containing the alpha 1 subunit among subsets of hippocampal interneurons, pointing to a pronounced functional specialization of these cells. Furthermore, the prominent expression of GABAA receptors by interneurons suggests that disinhibition may be of major functional relevance in regulating the balance between excitation and inhibition in hippocampal circuits.
通过分子克隆鉴定出多种GABAA受体亚基，这表明存在定位和功能特性不同的多种受体亚型。在本研究中，我们用亚基特异性抗血清免疫组织化学分析了大鼠海马中含α1亚基的GABAA受体的细胞分布。在海马角和齿状回中，许多中间神经元有明显的染色，这与锥体细胞和颗粒细胞树突层中中等程度的弥漫性免疫反应形成对比。用GABA抗体进行双重免疫荧光染色显示，海马中一部分GABA能神经元对α1亚基有免疫反应。为了确定这些细胞是否代表不同的中间神经元亚群，我们分析了GABAA受体α1亚基与海马中间神经元的选择性标记物（选定的钙结合蛋白和神经肽）的共定位。在海马角和齿状回中，所有小白蛋白阳性神经元和50%的钙视网膜蛋白阳性神经元都被双重标记，而含钙结合蛋白-D28k的中间神经元没有α1亚基染色。同样，大多数神经肽Y阳性神经元和一部分生长抑素阳性细胞被双重标记，而含胆囊收缩素和血管活性肠肽的细胞缺乏α1亚基染色。这些结果表明，在海马中间神经元亚群中，含α1亚基的GABAA受体存在细胞特异性表达，这表明这些细胞具有明显的功能特化。此外，中间神经元中GABAA受体的显著表达表明，去抑制在调节海马回路中兴奋与抑制之间的平衡方面可能具有主要的功能相关性。
