EXCITATORY SYNAPTIC TRANSMISSION IN EPILEPSY

很可能兴奋性突触的增强传递有助于 癫痫大脑的过度兴奋。 该项目将解决 这种可能性通过表征兴奋性突触传递， 点燃的动物 这些实验将检查突触传递在 海马体，大脑中特别容易发生癫痫的区域， 并将集中在CA 3锥体神经元，神经元兴奋性突触 容易出现过度兴奋，而RA是 海马三突触回路 我们将检查的两个突触是 齿状回颗粒神经元与海马CA3区神经元之间苔藓纤维突触 以及CA3神经元之间的联合连合突触。 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 在正常和点燃的动物中，在这些突触处诱发EPSC。 我们接下来 将测试点燃增强突触成分的假设， 通过检查NMDA型谷氨酸受体介导的 EPSC的药理学性质和EPSC的空间分布 突触后谷氨酸反应 最后，我们将确定 点燃通过突触后修饰改变突触传递 谷氨酸受体通过执行EPSC的量子分析。 这 分析将定义突触后和突触前的贡献， 点燃诱发的突触传递变化。 任何一个 突触前成分将通过测量突触前膜中的Ca信号来确定。 苔藓纤维终端和通过检查蛋白质的功能作用 可能对发射器释放很重要。

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.