Mechanisms of seizure propagation in limbic cortex

边缘皮层癫痫发作传播机制

• 批准号: 6823264
• 负责人: LEWIS B HABERLY
• 金额: $ 38.64万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6823264
• 关键词: Mechanisms; seizure; propagation; limbic; cortex

EXCEED THE SPACE PR_tBEB.. The proposed experiments use an in vivo model for partial epilepsy of temporal lobe origin to test hypotheses regarding the spread of seizure into normally functioning cortex from areas with epileptogenic abnormalities. Studies in vitro have identified many processes that are potentially involved; determining which of these are actually involved and how they contribute will require studies in intact animals that build on findings from in vitro analysis. The experiments will be performed on rat piriform cortex (PC) where partial seizures that secondarily generalize can be readily recruited in behaving animals by activity emanating from a small disinhibited focus. This same process can be duplicated under urethane anesthesia, enabling analytical study in vivo. Electrographic seizures are recruited when normal PC and adjoining limbic cortex are subjected to several seconds of low rate (3-4 Hz) rhythmic excitatory volleys generated by interictal-like discharges in a distant disinhibited focus. A detailed working hypothesis has been developed for the cascade of processes that underlies this transformation. Features of the hypothesis include: (1) K* plays a causal role for seizure spread into normal cortex (despite evidence to the contrary for seizure initiation). (2) Mechanisms for recruitment of seizure in hippocampus differ from those in most other limbic areas including PC. These stem from the lack of an inwardly rectifying cr channel (CIC-2) that regulates somatic-region CI- in hippocampal pyramidal cells but not in PC and many other limbic areas, and glial-like inwardly-rectifying K¿ channels that are weak or absent in hippocampal neurons but present in PC and other limbic areas. (3) Based on our findings from current source-density (CSD) analysis and transmembrane potential recordings in vivo, we propose that ephaptic-field transmission plays a central role in the generation of ictal activity by allowing high-rate, self-sustained discharges to occur after synaptic transmission is attenuated by depletion of docked synaptic vesicles and other factors. A key method is CSD analysis with a 22-site silicon probe that allows rapidly-evolving dendritic-region as well as somatic-region membrane currents to be visualized. Propagation of ephaptic-field driven discharges will be studied using new approaches for 2- and 3- dimensional CSD analysis. These experiments will provide essential information about the spread of epileptic activity into normal cortex, and clues concerning how this spread can be curtailed. PERFORMANCE SiTE ========================================Section End===========================================

超过了空间pr_tbeb ..拟议的实验使用体内模型进行部分癫痫临时叶的起源，以测试有关癫痫发作扩散到正常功能性皮质中的假设，从癫痫病异常的区域正常起作用。体外研究已经确定了许多潜在涉及的过程。确定实际涉及哪一个以及它们的贡献方式将需要在完整的动物中进行研究，这些动物以体外分析的发现为基础。实验将在大鼠梨状皮层（PC）上进行，其中部分癫痫发作可以通过从小小的抑制重点中发出的活动来轻易地在行为动物中募集。可以在氨基甲酸酯麻醉下复制相同的过程，从而使分析研究在体内。当正常的PC和毗邻的边缘皮层募集时，电气癫痫发作会受到低率（3-4 Hz）节奏的节奏兴奋性伏特利的几秒钟。已经为基础这种转变的过程级联发展了一个详细的工作假设。该假设的特征包括：（1）K*在癫痫发作中发挥因果作用，以扩散到正常皮层中（尽管有证据表明癫痫发作倡议的对比）。 （2）在海马中募集癫痫发作的机制与包括PC在内的大多数其他边缘区域不同。这些源于缺乏向内纠正的CR通道（CIC-2），该通道（CIC-2）调节了海马锥体细胞中的体细胞区域，但在PC和许多其他林木区域中没有，并且在PC和其他PC和其他Limbic区域中，在PC和许多其他林木区域中不存在薄弱的内置kSoceminter-Glial样的内部矫正通道。 （3）基于我们从当前源密度（CSD）分析和体内传播潜在记录的发现，我们提出，通过允许高速，自我维持的放电出现在ICTAL活动中的核心作用，从而使突触传播的高率，自我维持的放电在docked decked toss ne temaptic deckentic dectenenten decenenten dectenenten dectenenten dectenention dectenention deptenention deptenention降低了。一个关键方法是使用22个位点硅探针进行CSD分析，该探针允许可以看到快速发展的树突区域以及可以看到的体积区域膜电流。将使用2维和3维CSD分析的新方法研究以前场驱动排放的传播。这些实验将提供有关癫痫活性传播到正常皮层的基本信息，以及有关如何减少这种扩散的线索。性能站点====段end =====