The localization of GABAA receptors in mice with mutations affecting the structure and connectivity of the cerebellum.
The localization of GABAA receptors in mice with mutations affecting the structure and connectivity of the cerebellum.
复制标题
突变影响小脑结构和连接性的小鼠中 GABAA 受体的定位。
DOI：
10.1016/0006-8993(88)91480-1
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发表时间：
1988
期刊：
影响因子：
2.9
通讯作者：
Frostholm,A
中科院分区：
文献类型：
--
作者：
Rotter,A;Gorenstein,C;Frostholm,A
本文用放射自显影法研究了正常C57 BL/6 J小鼠和Weaver、Reeler、Purkinje细胞变性和Staggerer突变小鼠小脑[~ 3 H]蝇蕈醇结合位点的分布。在正常的79日龄小鼠小脑中，在颗粒细胞层中观察到最高浓度的[3 H]蝇蕈醇结合位点。在浦肯野细胞和分子层上存在低得多的颗粒密度，在小脑深部核和白色物质上观察到可忽略不计的结合位点。一个显着减少[3 H]蝇蕈醇标记观察到小脑皮质的81-86天的织布机突变体，这是最明显的，在蚓部的颗粒细胞损失是最大的。在颗粒细胞退化较少的半球上，仍然存在较高密度的结合位点。在27-29日龄的reeler小脑，浦肯野细胞错位，没有标记被视为超过深浦肯野细胞团。在准正常的表层皮质，标记密度超过存活的颗粒细胞层仅略有下降。在54-57日龄的浦肯野细胞变性突变体中，基本上所有的浦肯野细胞在第45天已经消失，观察到颗粒细胞层的颗粒密度降低了29%，而标记仍然存在于分子层中。几乎没有[3 H]蝇蕈醇标记检测超过任何部分的小脑皮层的25-27天的staggerer突变体（缺乏平行的纤维浦肯野细胞突触），虽然集群的存活颗粒细胞存在于显着的数量在侧面的皮质。我们的放射自显影数据表明，GABAA受体与颗粒细胞的分子和颗粒细胞层。此外，我们的研究结果提出的可能性，受体水平的维持可能依赖于颗粒细胞和其主要的突触后靶点，浦肯野细胞之间的突触接触。
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-day-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 GABAAreceptors 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.