SEIZURE MECHANISMS IN NEOCORTEX

研究计划的长期目标是回答 问题是， 通过正常大脑皮层的局灶性癫痫 具体来说， 神经递质发挥作用，细胞外的影响是什么？ 钾离子（K+）和神经元膜是否有变化 促进这一过程的特性？ 癫痫影响大约5%的人口。 的 局灶性癫痫发作如何传播的机制得到部分理解。 更彻底地解开机制将导致更好的 癫痫治疗中的治疗干预方法 患者 回答这些问题的工作将利用体外切片 哺乳动物的十字韧带皮层。 大V层锥体细胞 (Betz细胞）将被刺穿用于细胞内微电极 记录和单电极电压钳（SEVC）。 一些 研究还将使用特定的通道阻滞剂，离子取代 和神经递质的离子电渗疗法。 首先，兴奋性氨基对放电特性的影响 酸和神经肽将被研究和潜在的离子 用SEVC评估电流。 增加（K+）o对 放电特性和阈下离子电流及其对 递质释放和贝茨细胞对突触输入的反应将 同样要评价。 最后，将开发局灶性癫痫发作模型， 使用电刺激的新皮层切片。 贝茨细胞将 在癫痫发作之前，期间和之后进行研究，特别是观察 突触传递的变化，膜的改变 性质，以及（K+）对传播的影响。 通过正常的贝茨细胞进行癫痫发作。

The long term objectives of the research proposal are to answer the question, what are the mechanisms underlying the spread of focal seizures through normal neocortex? Specifically, what role do neurotransmitters play, what is the influence of extracellular potassium ions (K+) and are there changes in neuron membrane properties that facilitate the process? Epilepsy affects approximately 5% of the population. The mechanisms of how focal seizures spread are partially understood. A more complete unraveling of the mechanisms will lead to better methods of therapeutic intervention in the treatment of epileptic patients. Work towards answering these questions will utilize in vitro slices of mammalian pericruciate cortex. Large layer V pyramidal cells (Betz cells) will be impaled for intracellular microelectrode recording and single electrode voltage clamp (SEVC). Some studies will also use specific channel blocker, ionic substitutions and iontophoresis of neurotransmitters. Initially, the effects on firing properties of excitatory amino acids, and neuropeptides will be studied and the underlying ionic currents evaluated with SEVC. The effects of increased (K+)o on firing properties and subthreshold ionic currents and its effects on transmitter release and Betz cell response to synaptic input will likewise be evaluated. Finally, a model for focal seizures will be developed in the neocortical slices using electrical stimulation. Betz cells will be studied before, during and after seizures, specifically looking at changes in synaptic transmission, alterations of membrane properties, an the influence of (K+) on the propagation of the seizure activity through normal Betz cells.