Synaptically-induced sodium transients in glial cells

在大脑中的谷氨酸能突触，电生Na+依赖的谷氨酸转运体是终止传递和维持细胞外低水平谷氨酸的中心。这种转运蛋白在神经胶质细胞上高度表达。胶质细胞谷氨酸摄取失败会导致神经元之间兴奋性传递的改变，并与神经系统疾病有关。神经胶质谷氨酸转运体在突触中的功能作用及其与神经胶质谷氨酸受体激活的相互作用尚不清楚。在本项目中，我将使用双光子定量Na+成像结合全细胞膜片钳来分析外源性谷氨酸诱导的细胞内Na+瞬变和膜电流以及Bergmann神经胶质细胞精细突起中的突触活动。这些测量首次在Bergmann神经胶质细胞的不同细胞微域中对依赖Na+的谷氨酸运输、谷氨酸受体和它们的功能相互关系进行了生理定位。它们还将为我们理解Bergmann胶质细胞和小脑谷氨酸能突触上的Purkinje神经元之间的相互作用提供重要的见解。

At glutamatergic synapses in the brain, electrogenic Na+-dependent glutamate transporters are central for termination of transmission and for maintenance of low levels of extracellular glutamate. Such transporters are highly expressed on glial cells. Failure of glial glutamate uptake results in altered excitatory transmission between neurons and has been implicated in neurologic disease. The functional role of glial glutamate transporter at synapses and their interaction with glial glutamate receptor activation are not known in detail. In the present project, I will use quantitative two-photon Na+ imaging combined with whole-cell patch-clamp to analyse intracellular Na+ transients and membrane currents induced by exogenous glutamate application and synaptic activity in fine processes of Bergmann glial cells. These measurements allow for the first time a physiological mapping of Na+-dependent glutamate transport, glutamate receptors and and their funtional inter-relationsship in different cellular microdomains of Bergmann glial cells. They will also provide important insights into our understanding of the interaction between Bergmann glial cells and Purkinje neurons at glutamatergic synapses in the cerebellum.