EXCITATORY SYNAPTIC TRANSMISSION IN EPILEPSY

癫痫中的兴奋性突触传递

• 批准号: 6112170
• 负责人: GEORGE J. AUGUSTINE
• 金额: $ 22.94万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6112170
• 关键词: calcium flux; calmodulin dependent protein kinase; epilepsy; evoked potentials; flash photolysis; glutamate receptor; glutamates; granule cell; hippocampus; kindling; laboratory rat; neural transmission; neuropharmacology; pyramidal cells; receptor expression; synapses; synapsins; tissue /cell culture; voltage /patch clamp

It is likely that enhanced transmission at excitatory synapses contributes to the hyperexcitability of the epileptic brain. This project will address this possibility by characterizing excitatory synaptic transmission in kindled animals. The experiments will examine synaptic transmission in the hippocampus, a region of the brain particularly susceptible to seizures, and will focus on th excitatory synapses of CA3 pyramidal neurons, neurons that are prone to hyperexcitability and ra an essential part of the hippocampal trisynaptic circuitry. The two synapses we will examine are the "mossy fiber" synapse between dentate granule neurons and CA3 neurons and the associational-commisural synapse between CA3 neurons. We first will test the hypothesis that excitatory synaptic transmission is enhanced by kindling by comparing the properties of unitary postsynaptic currents (EPSCs) evoked at these synapses in normal and kindled animals. We next will test the hypothesis that kindling enhances the component of synaptic transmission mediated by NMDA-type glutamate receptors by examining the pharmacological properties of EPSCs and the spatial distribution of postsynaptic glutamate responses. Finally, we will determine whether kindling changes synaptic transmission via modification of postsynaptic glutamate receptors by performing a quantal analysis of EPSCs. This analysis will define the postsynaptic and presynaptic contributions to any kindling-induced changes in synaptic transmission. The locus of any presynaptic component will be determined by measuring Ca signals in the mossy fiber terminals and by examining the functional roles of proteins potentially important for transmitter release.

兴奋性突触的增强传输可能有助于 导致癫痫大脑过度兴奋。 该项目将解决 通过表征兴奋性突触传递来实现这种可能性 点燃的动物。 该实验将检查突触传递 海马体，大脑中特别容易癫痫发作的区域， 并将重点关注 CA3 锥体神经元、神经元的兴奋性突触 容易过度兴奋，并且是 海马三突触回路。 我们要检查的两个突触是 齿状颗粒神经元和 CA3 神经元之间的“苔藓纤维”突触 以及 CA3 神经元之间的关联连合突触。 我们首先 将检验兴奋性突触传递增强的假设 通过比较单一突触后电流的特性来点燃 （EPSC）在正常和点燃的动物的这些突触处被诱发。 我们接下来 将检验点火增强突触成分的假设 通过检查 NMDA 型谷氨酸受体介导的传输 EPSCs的药理学特性和空间分布 突触后谷氨酸反应。 最后，我们将确定是否 点燃通过突触后的修饰改变突触传递 通过对 EPSC 进行定量分析来检测谷氨酸受体。 这 分析将定义突触后和突触前对任何 点燃引起的突触传递变化。 任意的轨迹 突触前成分将通过测量 Ca 信号来确定 苔藓纤维末端并通过检查蛋白质的功能作用 对于发射机的释放可能很重要。