FUNCTION AND LOCALIZATION OF SYNAPTIC GLUTAMATE RECEPTOR

谷氨酸能突触是脑内最常见的兴奋性突触 中枢神经系统。除了他们在某些形式的 癫痫和兴奋性毒性，谷氨酸受体被认为与 依赖活动的发育过程和突触可塑性。 然而，人们对NMDA的生理行为知之甚少- 或AMPA亚型谷氨酸受体在新形成的突触或大约 这些突触的生理行为作为 发展。本提案中概述的问题解决了根本问题 需要研究的问题，以便更好地了解 谷氨酸受体、新形成的突触和突触发生过程。 这些实验将检查起作用的谷氨酸受体和 培养的大鼠海马神经元的谷氨酸能突触传递。 具体的目标是：1)确定生理上的差异 突触和突触外受体的群体；2)测定 谷氨酸受体聚集的内在要求在新- 形成突触；3)确定新形成突触的行为 关于谷氨酸受体的补体和释放概率。 第一个目标的结果将使我们能够监测 聚集并确定谷氨酸受体是否表现为突触表型 作为对实验操作的回应。第二个目标是确定 活性依赖突触形成中的致癌剂。调查结果： 最终目标本质上是有趣的，但它们也让我们问 海马细胞培养中突触的形成是随机的或 决定性的。

Glutamatergic synapses are the most prevelent excitatory synapses in the central nervous system. In addition to their roles in some forms of epilepsy and excitotoxicity, glutamate receptors have been implicated in activity-dependent developmental processes and synaptic plasticity. Little is known, however, about the physiological behavior of the NMDA- or AMPA-subtype glutamate receptors at newly-forming synapses or about the physiological behavior of these synapses as a function of development. The questions outlined in this proposal address fundamental issues that need to be examined in order for a better understanding of glutamate receptors, newly-formed synapses and synaptogenetic processes. The experiments will examine functioning glutamate receptors and glutamatergic synaptic transmission in cultured rat hippocampal neurons. The specific aims are: 1) determining physiological differences between populations of synaptic and extrasynaptic receptors; 2) determining the intrinsic requirements for clustering of glutamate receptors at newly- forming synapses; 3) determining the behavior of newly-forming synapses with respect to glutamate receptor complement and release probability. Results from the first aim will allow us to monitor the formation of clusters and determine if glutamate receptors show a synaptic phenotype in response to experimental manipulation. The second aim identifies the causitive agent in activity-dependent synapse formation. Results from the final aim are intrinsically interesting but they also allow us to ask if synapse formation in hippocampal cells in culture is stochastic or determinative.