MECHANISMS OF SEIZURES IN CORTICAL MICROGYRIA

描述（申请人的摘要）：几乎80%的被诊断患有 多小脑回症是大脑皮层的一种发育异常， 相关的癫痫发作障碍（Barkovich和Kjos，1992）。可惜这 癫痫的一种形式往往对手术或药物反应不佳。现在有 一种小脑回症的动物模型， 活性（Dvorak和Feit，1977; Jacobs等人，1996年）。小的冰冻损伤是 在正常新生大鼠的皮质表面上制造;这些导致破坏 深层皮质层和上面的层的压缩，产生一个凹痕， 或者说大脑皮层成熟后的微回。微回产生癫痫样 这是可以在体外受损新皮层切片中测量的活性。那里 关于突触和细胞机制的信息很少 慢性癫痫皮层下该提案的目的是利用 冷冻损伤模型，以探索突触和细胞的变化， 癫痫发作更具体地说，我们将记录从确定的兴奋性对 和抑制性神经元在第五层寻找1）在内在的变化， 单个神经元的膜特性，以及2）突触的变化 兴奋性-兴奋性、兴奋性-抑制性和 抑制性细胞对。此外，我们将寻找形态学 相关神经元轴突和树突分支模式的变化 癫痫样活动的产生。最后，我们将探讨 已知促进树突状分支的分子（cpg 15; Nedivi等， 1993）通过使用原位杂交，我们将尝试逆转任何 通过用截短的 form.的CPG 15。通过这种方式，我们希望阐明一些基本的 微脑回过度兴奋的机制，包括突触的程度， 和细胞重组。

DESCRIPTION (Applicant's Abstract): Almost 80% of adults diagnosed with polymicrogyria, a developmental abnormality of the cerebral cortex, have an associated seizure disorder (Barkovich and Kjos, 1992). Unfortunately, this form of epilepsy tends to respond poorly to surgery or medication. Now there is an animal model for microgyria that causes reproducible, focal, seizure-like activity (Dvorak and Feit, 1977; Jacobs et al., 1996). Small freeze lesions are made on the cortical surface of normal neonatal rats; these cause destruction of deep cortical layers and compression of the layers above, creating a dimple, or microgyrus once the cortex matures. The microgyrus produces epileptiform activity that can be measured in slices of lesioned neocortex in vitro. There is very little information about the synaptic and cellular mechanisms underlying chronically epileptic cortex. The goal of this proposal is to use the freeze lesion model to explore the synaptic and cellular changes that cause seizures. More specifically, we will record from identified pairs of excitatory and inhibitory neurons in layer V to look for 1) changes in the intrinsic membrane properties of individual neurons, and 2) changes in the synaptic coupling of excitatory-excitatory, excitatory-inhibitory, and inhibitory-inhibitory cell pairs. In addition, we will look for morphological changes in the axonal and dendritic branching patterns of the neurons involved in the generation of epileptiform activity. Finally, we will explore the role of a molecule known to promote dendritic arborization (cpg 15; Nedivi et al., 1993) by using in situ hybridization, and we will attempt to reverse any overarborization in the epileptic zone by viral vaccination with a truncated form. of cpg l5. In this way, we hope to elucidate some of the underlying mechanisms of hyperexcitability in microgyria, including the extent of synaptic and cellular reorganization.