DENTATE GYRUS CIRCUITRY IN TEMPORAL LOBE EPILESPY

描述：（改编自研究者摘要）：颞叶癫痫 癫痫是成人中最常见的癫痫形式，通常在医学上 难对付在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。齿状回的可能靶点是其他颗粒 细胞和GABA能中间神经元。与相邻颗粒细胞的接触将 会形成一个反复发作的兴奋回路从而引发癫痫接触 γ-氨基丁酸能中间神经元将加强具有 抗癫痫的效果这些选择并不相互排斥。这 该项目将确定颗粒细胞的连通性如何在 癫痫大脑具体的目的是确定突触的数量， 在红藻氨酸之前和之后形成的接触并识别突触后细胞 诱导颗粒细胞轴突重组。单个颗粒细胞将 用生物胞素在体内进行细胞内标记。在齿状回内， 将对完整的轴突进行三维重建和测量。使用 电子显微镜检查突触密度（每轴突长度的突触数量） 将测量选定轴突段的长度。轴突长度和突触数据 密度将被整合，以估计总数和分布 由单个颗粒细胞形成的突触。电子显微镜和后处理 将使用GABA的包埋免疫细胞化学来确定 GABA能神经元与非GABA能神经元形成的突触。这些 实验将提供关于颗粒细胞连接性的新数据， 建立一个实验方法来评估潜在的治疗设计 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.