MECHANISMS OF SEIZURE CONTROL IN LIMBIC CIRCUITS

(改编自申请人的摘要)： 研究项目是了解癫痫发作的机制和 使用大鼠边缘环路癫痫模型终止癫痫。 电生理学、药理学和组织化学技术将 被利用。本提案的具体目标有四个方面。 第一种假设是，癫痫发作是由大脑中的一种 抑制消失与兴奋增强相结合 导致脉冲通过神经元的传播增加 巡回赛。电生理学技术将检查 体内的兴奋和抑制，其中电路是完整的。这个 第二个假说是大脑通过大脑中的 释放内源性物质，如一氧化氮，在局部发挥作用 作为抗癫痫药。一氧化氮合酶抑制剂将接受测试 对癫痫发作和持续时间的影响。地点和电话号码 NADPH黄递酶阳性的神经元的数量将在 用组织化学技术反复发作。第三个假设 一次癫痫发作就会改变大脑的结构和功能 参与癫痫放电的电路，从而改变了 在相同的电路中引发随后的癫痫发作。中的更改 癫痫阈值，中间神经元数量的变化，发芽 苔藓样纤维和细胞死亡将在一次癫痫发作后确定。 最后一种假设是齿状回的固有特性是 足以表达癫痫发作，但输入到 齿状回调节癫痫发作的开始和终止。这将 在体外进行电生理测试，包括外源性和内源性 可以区分齿状回的性质。

(adapted from the applicant's abstract): The long-term goal of the research project is to understand the mechanisms of seizure onset and termination using a rat model of limbic-circuit seizures. Electrophysiological, pharmacological and histochemical techniques will be utilized. The specific aims of the present proposal are fourfold. The first hypothesis is that seizures are initiated in the brain by a combination of loss of inhibition and augmentation of excitation resulting in increased propagation of impulses through a neuronal circuit. Electrophysiological techniques will examine changes in excitation and inhibition in vivo where the circuits are intact. The second hypothesis is that the brain terminates seizure activity by the release of endogenous substances, such as nitric oxide, that act locally as antiepileptic agents. Nitric oxide synthase inhibitors will be tested for an effect on seizure onset and duration. The location and number of neurons that are NADPH-diaphorase positive will be determined after repeated seizures using histochemical techniques. The third hypothesis is that a single seizure alters the structure and function of the circuits involved in the seizure discharge, thus changing the probability of initiating a subsequent seizure in the same circuits. Changes in seizure threshold, changes in the interneuron population, sprouting of mossy fibers and cell death will be determined after a single seizure. The last hypothesis is that intrinsic properties of the dentate gyrus are sufficient to allow the expression of seizures, but inputs to the dentate gyrus regulate the onset and termination of seizures.This will be tested electrophysiologically in vitro where extrinsic and intrinsic properties of the dentate gyrus can be distinguished.