SEIZURE MECHANISMS IN NEOCORTEX

研究提案的长期目标是回答 问题是，病毒传播背后的机制是什么？ 通过正常的新皮质局灶性癫痫发作？具体地说，是什么角色 神经递质发挥作用了吗，细胞外的影响是什么 钾离子(K+)与神经细胞膜的变化 促进这一过程的物业？ 癫痫影响了大约5%的人口。这个 局灶性癫痫发作如何扩散的机制尚有部分了解。 更彻底地解开这些机制将导致更好的 癫痫的治疗干预方法 病人。 为回答这些问题所做的工作将利用体外切片 哺乳动物的十字核周皮质。大V层锥体细胞 (Betz细胞)将被刺入细胞内微电极 记录和单电极电压钳(SEVC)。一些人 研究还将使用特定的通道阻滞剂、离子替代品 神经递质的离子导入。 最初，对兴奋性氨基的激发性质的影响 酸和神经肽将被研究和潜在的离子 用SEVC评估电流。(K+)O升高对大鼠心脏功能的影响 激发特性和亚阈值离子电流及其对离子的影响 递质释放和Betz细胞对突触输入的反应将 同样也要接受评估。 最后，将在#年开发一个局灶性癫痫发作模型。 使用电刺激进行新皮质切片。贝茨细胞将成为 研究了癫痫发作前、发作中和发作后的情况，特别是 突触传递的改变，膜的改变 性质，以及(K+)对传播的影响 通过正常的Betz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.