LESION-INDUCED SYNAPTIC REORGANIZATION & EPILEPSY

损伤引起的突触重组

• 批准号: 3476943
• 负责人: THOMAS PETER SUTULA
• 金额: $ 8.52万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3476943
• 关键词: axon; brain electrical activity; denervation; electrophysiology; epilepsy; hippocampus; histochemistry /cytochemistry; innervation; laboratory rat; neuroanatomy; neurogenesis; sclerosis; synapses

Epilepsy is a common disorder of the central nervous system, and frequently develops in association with a variety of acquired neuropathological lesions. Kindling refers to the progressive increase in electrographic and behavioral seizures induced by repeated stimulation of certain neural pathways. Although kindling has attracted considerable interest as a model of epilepsy, fundamental issues about its cellular mechanisms and possible relationship to development of seizures after brain lesions are unresolved. Mesial temporal sclerosis (cell loss in hippocampal fields CA3-4 and CA1) is the most common structural lesion associated with epileptic seizures. Recent experiments (see PRELIMINARY STUDIES) have demonstrated that kindling of the entorhinal cortex is dramatically facilitated after destruction of CA3-CA4, a lesion that results in reactive synaptogenesis and reorganization of synaptic inputs to granule cells of the dentate gyrus, the major monosynaptic projection from the entorhinal cortex. This proposal will investigate the hypothesis that facilitated epileptogenesis after a lesion of CA3-CA4 is due to lesion-induced reorganization of hippocampal circuitry. The investigation will utilize quantitative histochemical methods, current source density analysis, and intracellular recording techniques. The proposed experiments will provide insight into epileptic mechanisms in the lesioned hippocampus, cellular mechanisms of kindling, effects of lesion-induced reorganization of synaptic inputs on excitability and integrative properties of dentate granule cells, and mechanisms of seizure development after brain injury.

癫痫是中枢神经系统的常见疾病， 经常与各种获得的合作发展 神经病理病变。 点燃是指进步的 增加的电图和行为癫痫发作 反复刺激某些神经途径。 虽然 作为一种模型，点燃引起了极大的兴趣 癫痫，有关其细胞机制的基本问题和 大脑之后癫痫发作的可能关系 病变尚未解决。 介质时间硬化症（海马场中的细胞损失CA3-4 CA1）是与 癫痫发作。 最近的实验（请参阅初步 研究）表明，肠道点燃 CA3-CA4破坏后，皮层很大程度上促进 导致反应性突触发生和重组的病变 对齿状回的颗粒细胞的突触输入（主要） 来自内嗅皮层的单突触投影。 这 提案将调查促进的假设 Ca3-Ca4病变后的癫痫发生是由于病变诱导的 海马电路的重组。 调查将 利用定量组织化学方法，电流源密度 分析和细胞内记录技术。 提议 实验将洞悉对癫痫机制 病变的海马，点燃的细胞机制，作用 病变引起的兴奋性突触输入的重组 以及齿状颗粒细胞的综合特性，以及 脑损伤后癫痫发育的机制。