MECHANISMS OF SEIZURE CONTROL IN LIMBIC CIRCUITS

开始于边缘结构的癫痫发作（部分复杂性癫痫发作）仍然存在 很难在人体内充分控制。一种动物模型， 复制这些癫痫发作是点燃，启动和 在点燃模型中终止后放电是未知的。近日一 与点燃癫痫发作有关的独特电生理事件已经被 在麻醉大鼠中识别，该事件被称为最大齿状回 激活，包括突然出现的大规模 齿状回颗粒细胞的群体峰电位。的 最大齿状激活的引发已经被证明是一个关键 海马后放电产生的步骤和 在点燃过程中发生的后放电的延长。长期 这个项目的目标是了解突触和细胞 最大齿状突起始和终止的机制 激活，因此，后放电。具体目标包括：1） 确定边缘回路内的解剖区域， 是产生和维持最大齿状激活所必需的， 2)确定神经递质或神经调质系统， 影响最大齿状激活的起始或持续时间，3） 确定最大齿状激活的细胞基础。的 实验使用体内和体外技术的组合来探索 这些地区在麻醉大鼠中的体内实验使用 多个细胞外记录和病变，以检查 边缘系统在控制最大齿状回中起关键作用 activation.在所有情况下，记录都是在齿状回进行的， 比较的目的。将使用药剂开始处理 神经递质/神经调质对启动的影响问题 和最大齿状激活的持续时间。药物增强和 抑制兴奋和抑制系统，以及改变 将测试胆碱能和腺苷能输入。大脑切片 包括海马体、下托和内嗅皮层， 检查最大齿状激活的细胞基础。

Seizures that begin in limbic structures (partial complex seizures) remain difficult to adequately control in humans. An animal model that closely replicates these seizures is kindling, The mechanisms that initiate and terminate after-discharges in the kindling model are unknown. Recently, a distinct electrophysiological event linked to kindled seizures has been identified in the anesthetized rat, This event is called maximal dentate activation and consists of the sudden appearance of bursts of large amplitude population spikes of the granule cells in the dentate gyrus. The elicitation of maximal dentate activation has been shown to be a critical step in the production of a hippocampal afterdischarge and in the lengthening of afterdischarges that occur during kindling. The long-term objectives of this project are to understand the synaptic and cellular mechanisms underlying the initiation and termination of maximal dentate activation and, therefore, afterdischarges. Specific aims include: 1) determination of the anatomical regions within the limbic circuit that are necessary for the generation and maintenance of maximal dentate activation, 2) determination of the neurotransmitter or neuromodulator systems that influence the initiation or duration of maximal dentate activation, 3) determination of the cellular basis of maximal dentate activation. The experiments use a combination of in vivo and in vitro techniques to explore these areas. The in vivo experiments in urethane-anesthetized rats use multiple extracellular recordings and lesions to examine the parts of the limbic system that are critical in the control of maximal dentate activation. In all instances recording is done in the dentate gyrus for comparison purposes. Pharmaceutical agents will be used to begin to address the issue of neurotransmitter/neuromodulator influence on the initiation and duration of maximal dentate activation. Drugs that potentiate and inhibit the excitatory and inhibitory systems, as well as agents that alter cholinergic and adenosinergic inputs will be tested. Brain slices that include the hippocampus, subiculum, and entorhinal cortex will be used to examine the cellular basis of maximal dentate activation.