Glutamate release and uptake at cerebellar synapses

描述（由申请人提供）：神经科学的一个基本原则是突触是大脑中的功能单位，因此也是心理学中的功能单位。每个突触的行为相对独立于它的邻居，因为它主要对自己释放的递质做出反应，而对邻居的递质要么根本没有反应，要么反应更少。突触囊泡的胞吐作用通常被认为只发生在超微结构定义的突触前活动区。如果这是真的，那么不在突触间隙内的受体必须被扩散出间隙的递质激活，或者根本不被激活。然而，AMPA受体介导的量子事件导致攀爬纤维释放记录在Bergmann胶质细胞在小脑皮质。这些量子事件是不一致的量子记录在邻近的浦肯野细胞接收输入从相同的攀爬纤维，因此，它似乎可以发生胞吐从异位攀爬纤维释放网站直接位于对面的伯格曼神经胶质细胞膜。如果异位释放是一种普遍现象，异突触和神经胶质细胞的相互作用更有可能是由于这种形式的串扰，而不是从突触裂缝内释放溢出实现的低浓度的递质。使用电生理学，光学和药理学的方法，我们将确定异位释放的特点，包括其钙依赖性，电压依赖性钙通道的类型提供必要的钙内流，释放概率，和异位释放突触前受体激活的敏感性，所有在传统的活动区释放相比。此外，我们将确定的优势，高浓度瞬变的递质在突触外空间，包括差异钙渗透性的AMPA受体和运动的Bergmann神经胶质过程的影响。

DESCRIPTION (provided by applicant): A basic tenet in neuroscience is that the synapse is the functional unit in the brain, and therefore in mentation. Each synapse acts relatively independently of its neighbors in that it primarily responds to its own released transmitter and either not at all or much less so to that of its neighbors. Exocytosis of synaptic vesicles is generally assumed to occur only at ultrastructurally defined presynaptic active zones. If this is true, receptors not located within the synaptic cleft must be activated by transmitter that diffuses out of the cleft, or not be activated at all. However, AMPA receptor-mediated quantal events resulting from climbing fiber release are recorded in Bergmann glial cells in the cerebellar cortex. These quantal events are not coincident with quanta recorded in neighboring Purkinje cells which receive input from the same climbing fiber and therefore it appears that exocytosis can occur from ectopic climbing fiber release sites located directly across from Bergmann glial membranes. If ectopic release is a general phenomenon, heterosynaptic and neural-glial interactions are more likely to result from this form of cross-talk rather than from the low concentrations of transmitter achieved by spillover from release within synaptic clefts. Using electrophysiological, optical, and pharmacological approaches, we will determine the characteristics of ectopic release including its calcium dependency, which types of voltage dependent calcium channels provide the necessary calcium influx, release probability, and the sensitivity of ectopic release to presynaptic receptor activation, all in comparison to release at conventional active zones. In addition, we will determine the advantages of high concentration transients of transmitter in the extrasynaptic space including differential calcium permeability of AMPA receptors and effects on motility of Bergmann glial processes.