EXCITATORY SYNAPTIC TRANSMISSION IN EPILEPSY

兴奋性突触的增强传递很可能对 癫痫患者大脑的过度兴奋性。该项目将解决 这种可能性通过表征兴奋性突触传递在 点燃的动物。这些实验将检查大脑中的突触传递。 海马体，大脑中一个特别容易癫痫发作的区域， 将集中在CA3锥体神经元的兴奋性突触，神经元 它们容易过度兴奋，并且是 海马区三突触回路。我们将研究的两个突触是 齿状颗粒神经元与CA3神经元之间的“苔藓纤维”突触 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 通过比较么正突触后电流的特性来点燃 (EPSCs)在正常和点燃的动物中诱发这些突触。我们是下一个 将检验点燃增强突触成分的假设 通过检测NMDA型谷氨酸受体介导的信号传导 EPSCs的药理特性及其空间分布 突触后谷氨酸反应。最后，我们将确定是否 点燃通过修饰突触后改变突触传递 通过对EPSCs进行量化分析来研究谷氨酸受体。这 分析将定义突触后和突触前对任何 点燃引起突触传递的改变。任何一个的轨迹 突触前成分将通过测量脑内钙信号来确定 苔藓纤维终末和通过检测蛋白质的功能作用 可能对发射机的释放很重要。

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.