IMMATURE HIPPOCAMPUS--EPILEPTOGENIC PROPERTIES

未成熟的海马——致癫痫特性

• 批准号: 2873134
• 负责人: John William Swann
• 金额: $ 25.73万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-06-29 至 2000-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2873134
• 关键词: NMDA receptors; action potentials; aging; amygdala; axon; cell age; confocal scanning microscopy; developmental neurobiology; electroencephalography; electrostimulus; epilepsy; evoked potentials; fluorescent dye /probe; hippocampus; kindling; laboratory rat; microelectrodes; neurogenesis; newborn animals; partial seizure; pyramidal cells; synapses; temporal lobe /cortex disorder; tissue /cell culture; video recording system; voltage /patch clamp

While much research has focused on the study of seizures in the mature nervous system, comparatively few attempts have been made to understand epileptogenesis in the developing brain. Numerous clinical and experimental studies support the notion that seizures early in life arise in ways that are different from those in adulthood. It is generally agreed that during certain critical periods in development the immature nervous system is unusually susceptible to seizures. The research proposed here is based on the observation that the CA3 subfield of slices taken from 1-2 week old rat hippocampus have a marked capacity to undergo electrographic seizures. Results suggest that age-dependent alterations in recurrent excitatory synaptic transmission contribute to differences in seizure susceptibility. Indeed, we propose that CA3 pyramidal cell recurrent axon collaterals and synapses undergo substantial remodeling during brain maturation. Early formed synapses appear to be replaced by a different complement of synapses in adulthood. Differences in synaptic physiology are likely to underlie enhanced seizure susceptibility in early life. Therefore, experiments are proposed that will directly compare local circuit excitation in immature (day 10-15) and mature (day 40-50) rat hippocampus. Electrophysiological properties of recurrent excitatory synapses will be examined in detail. We also plan to determine if neonatal amygdala kindling alters the recurrent collateral remodeling that normally takes place in early life. If CA3 network remodeling is a use-dependent process, then abnormal activation of hippocampal networks during kindling may lead to the persistence of excitatory synapses that would normally be eliminated with age. Such alterations in network development could conceivably underlie seizures in adulthood. Finally, recurrent excitatory synapse formation in slice cultures will be studied. Ultimately, these experiments will attempt to identify fundamental neurobiological processes that underlie recurrent excitatory synapse formation and selection. Taken together these multi- disciplinary studies are focused on understanding the ontogeny of local excitatory networks in hippocampus, how they contribute to seizures in early life, and whether experience-dependent modification of network development underlies some forms of temporal lobe epilepsy.

尽管很多研究都集中在成熟的癫痫发作的研究上 神经系统，尝试了解相对较少的尝试 发育中的大脑中的癫痫发生。 许多临床和 实验研究支持生命早期癫痫发作的观念 与成年的方式不同。 通常是 同意，在某些关键时期发展未成熟 神经系统异常容易受到癫痫发作。 研究 此处提出的是基于CA3切片子场的观察 从1-2周大的大鼠海马中占据 电图癫痫发作。 结果表明年龄依赖性改变 在复发性兴奋性突触传播中有差异 在癫痫发作的敏感性中。 确实，我们提出了CA3锥体细胞 复发的轴突侧支和突触经历了实质性的重塑 在大脑成熟期间。 早期形成的突触似乎被取代 成年中的突触的不同补充。 突触的差异 生理学可能是增强的癫痫发作易感性的基础 早期生活。 因此，提出了直接的实验 比较未成熟（第10-15天）和成熟的局部电路激发 40-50）大鼠海马。 复发的电生理特性 兴奋性突触将进行详细检查。 我们还计划 确定新生儿杏仁核点燃是否改变了反复的抵押品 改建通常发生在早期。 如果CA3网络 重塑是一个依赖使用的过程，然后是异常激活 点燃过程中的海马网络可能导致 兴奋性突触通常会随着年龄的增长而消除。 这样的 网络发展的改变可能是癫痫发作的基础 成年。 最后，在切片中复发性兴奋性突触形成 将研究文化。 最终，这些实验将尝试 确定基本的基本神经生物学过程 兴奋性突触的形成和选择。 结合了这些多重的 纪律研究的重点是理解局部的个体发育 海马的兴奋网络，它们如何促进癫痫发作 早期生活，以及是否依赖于网络的经验修改 发展是某些形式的颞叶癫痫的基础。