Rotter A, Gorenstein C, Frostholm A
Department of Pharmacology, California College of Medicine, University of California, Irvine 92717.
Brain Res. 1988 Jan 26;439(1-2):236-48. doi: 10.1016/0006-8993(88)91480-1.
The distribution of cerebellar [3H]muscimol binding sites was studied autoradiographically in normal C57BL/6J mice and in the weaver, reeler, Purkinje cell degeneration and staggerer mutant mice. In the normal 79-day-old mouse cerebellum, the highest concentration of [3H]muscimol binding sites was observed in the granule cell layer. A much lower grain density was present over the Purkinje cell and molecular layers and negligible numbers of binding sites were seen over the deep cerebellar nuclei and white matter. A significant decrease in [3H]muscimol labeling was observed over the cerebellar cortex of the 81-86-day-old weaver mutant; this was most pronounced in the vermis where granule cell loss was the greatest. Over the hemispheres, where fewer granule cells degenerate, a higher density of binding sites remained. In the 27-29-old reeler cerebellum, where Purkinje cells are malpositioned, no labeling was seen over the deep Purkinje cell masses. In the quasi-normal superficial cortex, labeling density over the surviving granule cell layer was only slightly decreased. In the 54-57-day-old Purkinje cell degeneration mutant, where essentially all Purkinje cells have disappeared by day 45, a 29% decrease in grain density over the granule cell layer was observed, while labeling was still present in the molecular layer. Virtually no [3H]muscimol labeling was detected over any part of the cerebellar cortex of the 25-27-day-old staggerer mutant (which lacks parallel fiber-Purkinje cell synapses), although clusters of surviving granule cells were present in significant numbers in the lateral aspects of the cortex. Our autoradiographic data indicate that GABAA receptors are associated with granule cells in both the molecular and granule cell layers. Furthermore, our results raise the possibility that the maintenance of receptor levels may be dependent upon synaptic contacts between the granule cell and its main postsynaptic target, the Purkinje cell.
采用放射自显影法研究了正常C57BL/6J小鼠以及weaver、reeler、浦肯野细胞变性和蹒跚突变小鼠小脑[3H]蝇蕈醇结合位点的分布情况。在正常79日龄小鼠小脑中，[3H]蝇蕈醇结合位点的最高浓度出现在颗粒细胞层。浦肯野细胞层和分子层的颗粒密度要低得多，在小脑深部核团和白质中可见的结合位点数量可忽略不计。在81 - 86日龄的weaver突变小鼠的小脑皮质中，观察到[3H]蝇蕈醇标记显著减少；在蚓部最为明显，那里颗粒细胞损失最大。在半球，颗粒细胞变性较少，结合位点密度较高。在27 - 29日龄的reeler小脑中，浦肯野细胞位置异常，在深部浦肯野细胞团中未见标记。在基本正常的浅层皮质中，存活颗粒细胞层的标记密度仅略有降低。在54 - 57日龄的浦肯野细胞变性突变小鼠中，到45日龄时基本上所有浦肯野细胞都已消失，颗粒细胞层的颗粒密度下降了29%，而分子层仍有标记。在25 - 27日龄的蹒跚突变小鼠（缺乏平行纤维 - 浦肯野细胞突触）的小脑皮质任何部位几乎都未检测到[3H]蝇蕈醇标记，尽管在皮质外侧有大量存活的颗粒细胞簇。我们的放射自显影数据表明，GABAA受体与分子层和颗粒细胞层中的颗粒细胞相关。此外，我们的结果增加了一种可能性，即受体水平的维持可能依赖于颗粒细胞与其主要突触后靶标浦肯野细胞之间的突触联系。
