SYNAPTIC MECHANISMS OF EPILEPTIFORM SYNCHRONIZATION

癫痫样同步的突触机制

• 批准号: 2267024
• 负责人: Paul A Rutecki
• 金额: $ 9.86万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-02-01 至 1995-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2267024
• 关键词: G protein; GABA receptor; afferent nerve; brain electrical activity; cell cell interaction; cyclic AMP; electrical conductance; electrical measurement; electrical potential; electrophysiology; experimental brain lesion; gamma aminobutyrate; hippocampus; laboratory rat; male; microelectrodes; neural plasticity; neural transmission; neuropharmacology; partial seizure; synapses

The hippocampus is susceptible to both physiological (the theta rhythm) and pathophysiological (epileptiform activity) forms of neuronal synchronization. This proposal intends to examine the synaptic mechanisms involved in the generation of abnormal epileptiform activity in the hippocampal slice preparation. The hippocampal slice can not have a behavioral seizure, but it can display abnormal neuronal synchronization that resembles ictal and interictal epileptiform discharges recorded in vivo. The slice preparation provides the opportunity to study the cellular physiology of epileptiform activity and permits the alteration of the extracellular environment. Intracellular studies have demonstrated the importance of synaptic mechanisms in the generation of the paroxysmal depolarizing shift (PDS), the intracellular correlate of the interictal discharge, which can be produced by reduction of synaptic inhibition mediated by GABA or the reduction of certain potassium currents. The PDS generated by either class of convulsants is comprised of synchronously occurring synaptic potentials and represents a network phenomenon. The goal of this proposal is to unravel the role of synaptic transmission in the expression and modulation of patterns of epileptiform activity (interictal and ictal). Experiments will use intracellular voltage- and current-clamp recording techniques and extracellular monitoring of the neuronal population response. The first specific aim is to relate the afterhyperpolarization that follows the PDS to the characteristics of spontaneous epileptiform activity as defined by the rate and duration of interictal discharges and the generation of ictal-like discharges. The second specific aim is to determine the contribution of synaptic transmission, particularly inhibitory synaptic transmission, in the generation of ictal patterns of synchronization. The third specific aim is to characterize the recurrent excitatory synaptic connections in the CA3 subfield after lesioning hippocampal afferents carried by the fornix (primarily commissural and cholinergic afferents), and define how the sequela of the lesion may increase the propensity for epileptiform synchronization. The underlying premise of this proposal is that by understanding epileptiform activity in the hippocampus, not only will the basis for clinical therapy of epilepsy be better designed, but also the synaptic mechanisms that contribute to normal synchronized neuronal activity may be better understood.

海马易受生理学（theta节奏）和 神经元的病理生理（癫痫病活性）形式 同步。该提案打算检查突触机制 参与在 海马切片准备。海马切片不能 行为癫痫发作，但可以显示异常的神经元同步 这类似于记录在 体内。切片制剂为研究细胞提供了机会 癫痫样活动的生理学，并允许改变 细胞外环境。细胞内研究表明 突触机制在阵发性的产生中的重要性 去极化偏移（PDS），间隔的细胞内相关性 放电，可以通过减少突触抑制产生 由GABA介导或减少某些钾电流。 PDS 两类的抽搐者生成 出现突触电位并代表网络现象。目标 该建议的是揭示突触传播在 癫痫样活性模式的表达和调节（间隔 和Ictal）。实验将使用细胞内电压和电流钳 记录技术和神经元细胞外监测 人口反应。第一个具体目的是联系 遵循PD的超极化 自发性癫痫样活性由速率和持续时间定义 间排出和产生类似ICTAL的排放。这 第二个特定目的是确定突触的贡献 传播，特别是抑制性突触传播 同步的发作模式产生。第三个具体目的是 为了表征CA3中的复发性兴奋性突触连接 病变后的海马传入后的子场 （主要是合理和胆碱能传入），并定义如何 病变的后遗症可能会增加癫痫样的倾向 同步。该提议的基本前提是 了解海马中的癫痫样活动，不仅会 癫痫临床治疗的基础是更好地设计的 有助于正常同步神经元的突触机制 活动可以更好地理解。