Mechanisms of seizure propagation in limbic cortex

边缘皮层癫痫发作传播机制

基本信息

批准号：
7156913
负责人：
LEWIS B HABERLY
金额：
$ 36.64万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-12-01 至 2010-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7156913
关键词：
3-Dimensional Action Potentials Anesthesia procedures Animals Anticonvulsants Area Attention Attenuated Automobile Driving Buffers Clinical Complement component C1s Complex Data Development Disruption Distant Docking Effectiveness Electrodes Elevation Epilepsy Equilibrium Feedback Fiber Focal Seizure Gap Junctions Generations Goals Hippocampus (Brain)In Vitro Mediating Membrane Membrane Potentials Methods Modeling Neurons Numbers Pathway interactions Play Preparation Process Pyramidal Cells Rate Rattus Receptor Activation Recruitment Activity Role Seizures Silicon Site Slice Source Staging Stimulus Synapses Synaptic Transmission Synaptic Vesicles Temporal Lobe Temporal Lobe Epilepsy Terminology Testing Urethane Work awake base density extracellular in vivo in vivo Model inward rectifier potassium channel novel strategies piriform cortex research study response restraint stem transmission process two-dimensional voltage gated channel

项目摘要

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.

pr_tbeb .. 提出的实验使用体内模型进行临时叶的部分癫痫进行测试假设癫痫发作传播到正常发挥作用的皮质中的假设异常。体外研究已经确定了许多潜在涉及的过程。确定实际涉及哪些以及它们的贡献方式将需要在完整动物中进行研究关于体外分析的发现。实验将在部分部分进行大鼠梨状皮层（PC）上进行次级概括的癫痫发作可以通过从中发出的活动来轻易地在行为动物中招募一个小的抑制重点。可以在尿烷麻醉下重复同样的过程，从而实现分析研究在体内。当正常的PC和毗邻的边缘皮层时，电气癫痫发作将招募经过几秒钟的低率（3-4 Hz）节奏兴奋性凌空动物在遥远的抑制重点中放电。为此开发了一个详细的工作假设这一转变的基础的过程级联。假设的特征包括：（1）k*扮演A 癫痫发作的因果作用扩散到正常皮层中（尽管有证据表明癫痫发作倡议的对比）。（2）海马招募癫痫发作的机制与大多数其他边缘地区不同的机制不同个人电脑。这些源于缺乏向内纠正CR通道（CIC-2）调节体细胞区域的CR通道（CIC-2）在海马锥体细胞中，但在PC和许多其他边缘区域中不在在海马神经元中但PC和其他边缘区域中存在弱或不存在的K键。（3）根据我们从当前源密度（CSD）分析和跨膜电势记录的发现在体内，我们提出，在通过通过部署减弱突触传输后，允许高速，自我维持的排放发生停靠的合成蔬菜和其他因素。一个关键方法是用22个硅证明的CSD分析这样可以将快速发展的树突区域以及体细胞膜电流可视化。将使用2-和3-- 维度CSD分析。这些实验将提供有关传播的基本信息癫痫活性到正常的皮层中，以及有关如何减少这种扩散的线索。

项目成果

期刊论文数量（23）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Characterization of synaptically mediated fast and slow inhibitory processes in piriform cortex in an in vitro slice preparation.

体外切片制备中梨状皮层突触介导的快速和慢速抑制过程的表征。

DOI：
10.1152/jn.1988.59.5.1352
发表时间：
1988
期刊：
Journal of neurophysiology
影响因子：
2.5
作者：
Tseng,GF;Haberly,LB
通讯作者：
Haberly,LB

Layer-specific properties of the transient K current (IA) in piriform cortex.

梨状皮层瞬态 K 电流 (IA) 的层特定特性。

DOI：
10.1523/jneurosci.16-12-03862.1996
发表时间：
1996
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience.
影响因子：
0
作者：
Banks,MI;Haberly,LB;Jackson,MB
通讯作者：
Jackson,MB

Regulation of the NMDA component of EPSPs by different components of postsynaptic GABAergic inhibition: computer simulation analysis in piriform cortex.

突触后 GABA 能抑制的不同成分对 EPSP 的 NMDA 成分的调节：梨状皮层的计算机模拟分析。