Douyard Jessica, Shen Lei, Huganir Richard L, Rubio Maria E
Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 062693156, USA.
J Comp Neurol. 2007 May 1;502(1):141-56. doi: 10.1002/cne.21294.
In neurons, AMPA glutamate receptors are developmentally regulated and selectively targeted to synaptic sites. Astroglial cells also express AMPA receptors, but their developmental pattern of expression and targeting mechanisms are unknown. In this study we investigated by immunocytochemistry at the light and electron microscopy level the expression of GluR1 and its scaffolding proteins SAP97 (synapse-associated protein) and 4.1N during cerebellar development. In cerebellar cortex the GluR1 AMPA receptor subunit is expressed exclusively in Bergmann glia in the adult rodent. Interestingly, we observed that GluR1 was expressed postsynaptically at the climbing fibers (CF) synapse at early ages during Purkinje cell dendritic growth and before the complete ensheathment of CF/Purkinje cell synapses by Bergmann glia. However, its expression changed from neurons to Bergmann glia once these glial cells had completed their enwrapping process. In contrast, GluR2/3 and GluR4 AMPAR subunits were stably expressed in both Purkinje cells (GluR2/3) and Bergmann glia (GluR4) throughout postnatal development. Our data indicate that GluR1 expression undergoes a developmental switch from neurons to glia and that this appears to correlate with the degree of Purkinje cell dendritic growth and their enwrapping by Bergmann glia. SAP97 and 4.1N were developmentally regulated in the same pattern as GluR1. Therefore, SAP97 and 4.1N may play a role in the transport and insertion of GluR1 at CF/Purkinje cell synapses during early ages and at Bergmann glia plasma membrane in the adult. The parallel fiber (PF)/Purkinje cell synapse contained GluR2/3 but lacked GluR1, SAP97, and 4.1N at the time of PF synaptogenesis.
在神经元中，AMPA 谷氨酸受体在发育过程中受到调控，并选择性地定位于突触部位。星形胶质细胞也表达 AMPA 受体，但其发育表达模式和靶向机制尚不清楚。在本研究中，我们通过光镜和电镜免疫细胞化学方法，研究了小脑发育过程中 GluR1 及其支架蛋白 SAP97（突触相关蛋白）和 4.1N 的表达情况。在成年啮齿动物的小脑皮质中，GluR1 AMPA 受体亚基仅在伯格曼胶质细胞中表达。有趣的是，我们观察到在浦肯野细胞树突生长的早期阶段以及伯格曼胶质细胞完全包裹攀爬纤维（CF）/浦肯野细胞突触之前，GluR1 在 CF 突触的突触后部位表达。然而，一旦这些胶质细胞完成包裹过程，其表达就从神经元转变为伯格曼胶质细胞。相比之下，在整个出生后发育过程中，GluR2/3 和 GluR4 AMPAR 亚基在浦肯野细胞（GluR2/3）和伯格曼胶质细胞（GluR4）中均稳定表达。我们的数据表明，GluR1 的表达经历了从神经元到胶质细胞的发育转变，这似乎与浦肯野细胞树突生长的程度及其被伯格曼胶质细胞包裹的程度相关。SAP97 和 4.1N 的发育调控模式与 GluR1 相同。因此，SAP97 和 4.1N 可能在早期 CF/浦肯野细胞突触处以及成年期伯格曼胶质细胞质膜上 GluR1 的运输和插入过程中发挥作用。在平行纤维（PF）/浦肯野细胞突触形成时，该突触含有 GluR2/3，但缺乏 GluR1、SAP97 和 4.1N。
