DENTATE GYRUS CIRCUITRY IN TEMPORAL LOBE EPILESPY

描述：(改编自《调查者摘要》)：颞叶癫痫 是成人中最常见的癫痫形式，在医学上通常是 很难对付。颞叶癫痫患者的齿状回 颗粒细胞轴突重组。颗粒细胞轴突的新突触靶点 必须被识别出来。齿状回中可能的靶点是其他颗粒。 细胞和GABA能中间神经元。与邻近颗粒细胞的接触将 形成一种可导致癫痫发作的反复兴奋回路。联系方式： GABA能中间神经元将加强反复的抑制回路 一种抗癫痫作用。这些替代方案并不是相互排斥的。这 项目将确定颗粒细胞的连接性如何在 癫痫样的大脑。具体目标是定义突触的数量 海人酸化前后突触形成和突触后细胞的识别 诱导颗粒细胞轴突重组。单个颗粒细胞将是 在体内用生物细胞素标记细胞内。在齿状回内 完整的轴突将被三维重建和测量。vbl.使用 电子显微镜观察突触密度(每轴突长度的突触数) 将测量所选轴突节段的大小。轴突长度和突触的数据 密度将被综合来估计总数量和分布 由单个颗粒细胞形成的突触。电子显微镜和POST 将使用GABA包埋免疫细胞化学来确定比例 由GABA能神经元与非GABA能神经元形成的突触的比较。这些 实验将提供有关颗粒细胞和 建立评估设计的潜在治疗方法的实验方法 影响颗粒细胞轴突重组。

DESCRIPTION: (Adapted from the Investigator's Abstract): Temporal lobe epilepsy is the most common form of epilepsy in adults, and it is often medically intractable. In the dentate gyrus of patients with temporal lobe epilepsy granule cell axons reorganize. The new synaptic targets of granule cell axons must be identified. The possible targets in the dentate gyrus are other granule cells and GABAergic interneurons. Contacts with neighboring granule cells will form a recurrent excitatory circuit that could generate seizures. Contacts with GABAergic interneurons will strengthen the recurrent inhibitory circuit having an anti-epileptic effect. These alternatives are not mutually exclusive. This project will determine how the connectivity of granule cells changes in the epileptic brain. The specific aims are to define the number of synaptic contacts formed and identify the postsynaptic cells before and after kainate induced granule cell axon reorganization. Individual granule cells will be labeled intracellularly in vivo with biocytin. Within the dentate gyrus their complete axon arbors will be 3-dimensionally reconstructed and measured. Using electron microscopy the synaptic density (number of synapses per axon length) of selected axon segments will be measured. Data on axon length and synapse density will be integrated to estimate the total number and distribution of synapses made by individual granule cells. Electron microscopy and post embedding immunocytochemistry for GABA will be used to determine the proportion of synapses formed with GABAergic versus non-GABAergic neurons. These experiments will provide new data on the connectivity of granule cells and establish an experimental approach for evaluating potential treatments designed to influence granule cell axon reorganization.