MECHANISMS OF SEIZURE CONTROL IN LIMBIC CIRCUITS

（摘自申请人摘要）： 研究项目是了解癫痫发作的机制， 终止使用大鼠模型的边缘电路癫痫发作。 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。 第一个假设是癫痫发作是由大脑中的 抑制丧失和兴奋增强的组合 导致通过神经元的脉冲传播增加 电路. 电生理学技术将检查 兴奋和抑制在体内的电路是完整的。 的 第二个假设是，大脑终止癫痫活动的 内源性物质的释放，如一氧化氮，在局部起作用 作为抗癫痫药。将测试一氧化氮合酶抑制剂 对癫痫发作和持续时间的影响。 地点和号码 NADPH-黄递酶阳性的神经元将在 反复发作的组织化学技术。 第三个假设 一次癫痫发作会改变大脑皮层的结构和功能， 参与癫痫放电的电路，从而改变了 在相同的回路中引发随后的癫痫发作。 变化 癫痫发作阈值，中间神经元数量的变化， 苔藓纤维和细胞死亡将在单次发作后确定。 最后一个假设是齿状回的内在特性是 足以让癫痫发作的表达，但输入到 齿状回调节癫痫发作和终止。这将 在体外进行电生理学测试， 可以区分齿状回的特性。

(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.