IMMATURE HIPPOCAMPUS--EPILEPTOGENIC PROPERTIES

未成熟的海马——致癫痫特性

• 批准号: 2332930
• 负责人: John William Swann
• 金额: $ 20.97万
• 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/2332930
• 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.

虽然许多研究都集中在成熟人群的癫痫发作研究上 神经系统，相对较少的尝试来理解 发育中的大脑中的癫痫发生。 众多临床和 实验研究支持癫痫发作在生命早期就出现的观点 以与成年时不同的方式。 一般是 一致认为，在发展的某些关键时期，不成熟的 神经系统异常容易癫痫发作。 研究 这里提出的建议是基于切片的 CA3 子域的观察 取自 1-2 周大的大鼠海马体，具有显着的承受能力 电图癫痫发作。 结果表明，年龄依赖性的改变 周期性兴奋性突触传递导致差异 癫痫易感性。 事实上，我们认为 CA3 锥体细胞 循环轴突侧支和突触经历实质性重塑 在大脑成熟过程中。 早期形成的突触似乎被 成年期突触的不同补充。 突触差异 生理学可能是癫痫易感性增强的基础 早期生活。 因此，建议进行实验，直接 比较未成熟（第 10-15 天）和成熟（第 15 天）的本地电路激励 40-50) 大鼠海马体。 复发性电生理特性 将详细检查兴奋性突触。 我们还计划 确定新生儿杏仁核点燃是否会改变循环性侧支循环 通常发生在生命早期的重塑。 如果CA3网络 重塑是一个依赖于使用的过程，那么异常激活 点燃期间的海马网络可能会导致持续存在 兴奋性突触通常会随着年龄的增长而消失。 这样的 可以想象，网络发展的改变可能是缉获的原因 成年期。 最后，切片中反复兴奋性突触的形成 将研究文化。 最终，这些实验将试图 确定复发性基础的基本神经生物学过程 兴奋性突触的形成和选择。 综合这些多 学科研究的重点是了解当地的个体发育 海马体的兴奋性网络，它们如何促进癫痫发作 早期生活，以及网络是否依赖于经验的修改 某些形式的颞叶癫痫的发展是其基础。