EXCITATORY TRANSMISSION IN TEMPORAL LOBE EPILEPSY

了解苔藓纤维发芽的功能作用， 癫痫 患者是开发这种疾病新疗法的关键。 先前的研究已经利用低分辨率的细胞外和细胞外基质。 细胞内记录，以研究苔藓的功能作用 纤维 发芽 该提案概述了一项战略， 决议 兴奋性突触后全细胞电压钳记录 电流 （EPSC）在颗粒细胞诱发的电和 光刺激功能性兴奋的发生率和程度 将在正常条件下研究颗粒细胞之间的突触 条件和随后苔藓纤维发芽的制剂 增加难度和复杂性：1）红藻氨酸处理 器官型 海马切片培养物和分离的急性海马切片 （2） 毛果芸香碱处理的大鼠;和3）人癫痫海马。 的 经常性兴奋性突触连接的性质将是 检查 通过确定由免疫调节剂介导的EPSC复发的比例， 由NMDA 和非NMDA谷氨酸受体。 GABA能的作用 传输 对复发性EPSC也将进行调查。 这些实验 是 旨在确定是否颗粒细胞从功能 复发性 苔藓纤维后与其他颗粒细胞的兴奋性突触 发芽和定义这些经常性的属性 兴奋性 突触连接

Understanding the functional role of mossy fiber sprouting in epileptic patients is pivotal in developing new therapies for this disease. Previous studies have utilized low resolution extracellular and intracellular recording to investigate the functional role of mossy fiber sprouting. This proposal outlines a strategy to use high resolution whole cell voltage clamp recording of excitatory postsynaptic currents (EPSCs) in granule cells evoked with both electrical and photostimulation. The incidence and extent of functional excitatory synapses between granule cells will be investigated under normal conditions and following mossy fiber sprouting in preparations of increasing difficulty and complexity: 1) Kainic acid treated organotypic hippocampal slice cultures; and acute hippocampal slices isolated from 2) Pilocarpine treated rats; and 3) Human epileptic hippocampus. The properties of recurrent excitatory synaptic connections will be examined by determining the proportion of recurrent EPSCs that is mediated by NMDA and nonNMDA glutamate receptors. The effects of GABAergic transmission on recurrent EPSCs also will be investigated. These experiments are designed to determine whether granule cells from functional recurrent excitatory synapses with other granule cells following mossy fiber sprouting and to define the properties of these recurrent excitatory synaptic connections.