MECHANISMS OF SEIZURE CONTROL IN LIMBIC CIRCUITS

边缘系统的癫痫发作控制机制

• 批准号: 2796976
• 负责人: Janet Lynn Stringer
• 金额: $ 6.8万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1999-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2796976
• 关键词: cell death; dentate gyrus; electrophysiology; epilepsy; histochemistry /cytochemistry; interneurons; laboratory rat; limbic system; mossy fiber; neural conduction; neuroanatomy; neuropharmacology; neurophysiology; nitric oxide; nitric oxide synthase

(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.

（改编自申请人的摘要）： 研究项目是了解癫痫发作的机制和 使用边缘电路癫痫发作的大鼠模型终止。 电生理，药理和组织化学技术将 被利用。 本提案的具体目的是四倍。 第一个假设是，癫痫发作是通过一个 抑制丧失和激发的增强的结合 导致通过神经元的脉冲传播增加 电路。 电生理技术将检查 电路完好无损的体内激发和抑制作用。 这 第二个假设是大脑通过 在局部起作用的内源性物质，例如一氧化氮 作为抗癫痫剂。一氧化氮合酶抑制剂将进行测试 为了影响癫痫发作和持续时间。 位置和数字 将在 使用组织化学技术重复癫痫发作。 第三个假设 是一个癫痫发作改变了 癫痫发射涉及的电路，从而改变了概率 在同一电路中启动随后的癫痫发作。 变更 癫痫发作阈值，中间神经元人口的变化，发芽 苔藓纤维和细胞死亡将在一次癫痫发作后确定。 最后一个假设是齿状回的内在特性是 足以允许癫痫发作的表达，但输入到 齿状回调节癫痫发作和终止。 在体外进行电生理测试，外部和内在 可以区分齿状回的特性。