PHYSIOLOGY OF EPILEPTOGENESIS IN PIRIFORM CORTEX

梨状皮层癫痫发生的生理学

• 批准号: 2263691
• 负责人: LEWIS B HABERLY
• 金额: $ 22.2万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-09-01 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2263691
• 关键词: bicuculline; brain electrical activity; cerebral cortex; convulsants; electron microscopy; epilepsy; evoked potentials; histology; laboratory rat; lateral olfactory area; microscopy; neural inhibition; neural initiation; neuroanatomy; neurophysiology; picrotoxin; pyramidal cells

The goal is to contribute to the understanding of neuronal interactions that underlie seizure activity in the cerebral cortex. Piriform cortex will be used for the proposed experiments because it is highly susceptible to epileptogenesis, may play an important role in temporal lobe epilepsy, and has structural, physiological, and pharmacological features that qualify it as a model system for study of cerebral cortex. The proposed experiments will focus on long-lasting "induction" processes that are believed to be involved in the development and progression of some forms of epilepsy, and on neuronal mechanisms that underlie spread of seizure activity from epileptic foci. Studies of long-lasting induction processes will be carried out by physiological analysis of the chances that underlie the development of epileptiform EPSPs in slices of piriform cortex subjected to bursting activity, and in slices from rats in which epilepsy has been "kindled" by repeated shock stimulation. Previous studies have localized the neurons in which the induced changes take place; in the proposed studies hypotheses concerning the identity of these changes will be tested using intracellular recording techniques. Studies of the mechanism of spread of epileptiform activity will be carried out on an anaesthetized rat preparation in which interictal- and ictal-like epileptiform activity spreads throughout the piriform cortex and adjacent cortical areas when a pharmacologically disinhibited focus is repetitively activated by 1 or 2 Hz shock stimulation. The hypothesis will be tested that repetitive bursting activity conducted from the focus by association axons induces a transient reduction in inhibitory processes in the surrounding cortex, thereby initiating a slow regenerative spread of epileptiform activity. Changes will be analyzed in each of the 4 inhibitory processes that have been identified. These studies will employ intracellular recording and current source-density analysis techniques in an anaesthetized rat preparation. Current source-density analysis gives a graphic picture of the sequence of neuronal events over depth and time via mathematical analysis of extracellularly recorded field potentials. To assist in interpretation of the physiological results, both local axon collateral systems and projection pathways that are believed to be involved in the induction and spread of seizure activity will be studied morphologically. Techniques to be used include intracellular injection of biocytin in slices maintained in vitro, and extracellular injection of Phaseolus vulgaris leucoagglutinin (PHA-L) in intact animals.

目的是为理解神经元相互作用做出贡献 这是大脑皮层癫痫发作活性的基础。梨状皮层会 用于提议的实验，因为它非常容易受到影响 癫痫发生，可能在颞叶癫痫中起重要作用，并且 具有结构性，生理和药理特征，可以使其有资格 作为研究大脑皮质的模型系统。提出的实验 将专注于被认为是的持久“归纳”过程 参与某些形式的癫痫的发展和发展，以及 关于神经元机制，这些机制是癫痫发作活性从 癫痫病灶。将进行长期诱导过程的研究 通过生理分析对发展的机会的机会 在梨状皮层切片中的癫痫样EPSP的爆发 活动，以及在大鼠的切片中，癫痫已被“点燃” 反复的冲击刺激。先前的研究已将神经元定位在 引起的变化发生了；在拟议的研究中假设 关于这些变化的身份，将使用细胞内测试 记录技术。研究癫痫样的传播机制 活动将在麻醉的大鼠制剂上进行，其中 间歇性和无症状的癫痫样活性扩散在整个 当药理学时，梨状皮层和邻近皮质区域 DISINBIND焦点被1或2 Hz冲击重复激活 刺激。该假设将测试重复爆发 缔合轴突从焦点进行的活性诱导了瞬态 降低周围皮质中的抑制过程 引发癫痫样活性的缓慢再生扩散。更改 将在已有的四个抑制过程中的每个过程中进行分析 确定。这些研究将采用细胞内记录和电流 源密度分析技术在麻醉大鼠制备中。 当前的源密度分析给出了序列的图形图片 通过数学分析对深度和时间的神经元事件 细胞外记录的场电位。协助解释 生理结果，包括局部轴突侧支系统和 被认为与归纳有关的投射途径和 癫痫活性的传播将在形态上研究。技术 使用包括在维持的切片中的细胞内注射生物细胞 体外和细胞外反射叶谷谷蛋白 （PHA-L）完整动物。