Frostholm A, Rotter A
Department of Pharmacology, California College of Medicine, University of California, Irvine 92717.
Brain Res. 1987 Dec 15;465(1-2):157-66. doi: 10.1016/0165-3806(87)90237-9.
The characteristics of [3H]muscimol binding were investigated in cerebellar sections from 7-day-old mice. The binding sites were found to possess the kinetic properties and pharmacological specificity characteristic of high-affinity GABAA receptors. [3H]Muscimol binding sites in the developing C57BL/6J mouse cerebellum were visualized by light microscopic autoradiography. A distinct band of labeling situated over the molecular layer was apparent from day 1 to day 7. The external granule cell layer remained unlabeled throughout development. Labeling over the internal granule cell layer gradually increased from birth; it became more dense and well defined until adult levels of grain density were reached at 35-42 days of age. The deep cerebellar nuclei were moderately labeled at birth and gradually decreased in density thereafter. The observed ontogeny of granule cell [3H]muscimol binding sites suggests that the synthesis of receptors is initiated at a time immediately after cessation of cell division, coinciding with the beginning of granule cell translocation across the molecular layer. Since, at this time, granule cells have not yet formed synapses with the GABAergic Golgi II cells, nor have they, in turn, formed the vast majority of synaptic contacts with Purkinje cells, it follows that receptor appearance precedes the formation of afferent connections, and may also precede efferent synaptic contacts. The timing of the appearance of [3H]muscimol binding sites raises the possibility that their initial acquisition may be related to developmental events other than the interaction of the granule cell with its pre- or postsynaptic neuronal partners.
研究了7日龄小鼠小脑切片中[³H]蝇蕈醇结合的特性。发现结合位点具有高亲和力GABAA受体的动力学特性和药理学特异性。通过光学显微镜放射自显影观察发育中的C57BL/6J小鼠小脑中的[³H]蝇蕈醇结合位点。从第1天到第7天，分子层上方出现一条明显的标记带。整个发育过程中，外颗粒细胞层未被标记。内颗粒细胞层的标记从出生时开始逐渐增加；在35 - 42日龄达到成年水平的颗粒密度之前，它变得更加密集且清晰。小脑深部核团在出生时被中度标记，此后密度逐渐降低。观察到的颗粒细胞[³H]蝇蕈醇结合位点的个体发生表明，受体的合成在细胞分裂停止后立即开始，这与颗粒细胞穿过分子层的迁移开始时间一致。由于此时颗粒细胞尚未与GABA能高尔基II细胞形成突触，反过来也尚未与浦肯野细胞形成绝大多数突触联系，因此受体的出现先于传入连接的形成，也可能先于传出突触联系。[³H]蝇蕈醇结合位点出现的时间提出了一种可能性，即它们的最初获得可能与颗粒细胞与其突触前或突触后神经元伙伴相互作用之外的发育事件有关。
