SYNAPTIC MECHANISMS OF EPILEPTIFORM SYNCHRONIZATION

海马体对生理性(theta节律)和 神经元的病理生理学形式(癫痫样活动) 同步。这项提议意在研究突触机制。 参与脑内异常癫痫样活动的产生 海马区脑片制备。海马片不能有 行为发作，但可显示异常神经元同步性 类似于发作期和发作期癫痫样放电 活着。切片的制备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， 突触机制在阵发性发作发生中的重要性 去极化漂移(PDS)，发作间期的细胞内相关性 放电，可通过减少突触抑制而产生 由GABA或某些钾电流的减少所介导。PDS 由任一类惊厥药产生的 出现突触电位，代表一种网络现象。目标是 这一建议的目的是揭示突触传递在脑内的作用 癫痫样活动模式的表达和调节(发作间期 和发作期)。实验将使用细胞内电压和电流钳位 神经元的记录技术和细胞外监测 人口反应。第一个具体目标是将 后超极化，遵循PDS的特征 自发性癫痫样活动由发作频率和持续时间定义 发作间期放电和发作性放电的产生。这个 第二个具体目标是确定突触的贡献 突触传递，尤其是抑制性突触传递 发作期同步模式的产生。第三个具体目标是 CA3区复发性兴奋性突触联系的特征 穹隆携带的海马区传入神经损毁后的亚场 (主要是连合和胆碱能传入)，并定义 病变的后遗症可能会增加癫痫样的倾向。 同步。这项提议的基本前提是通过 了解海马区的癫痫样活动，不仅将 为癫痫的临床治疗提供更好的设计依据，也是 有助于正常同步化神经元的突触机制 人们可能会更好地理解这些活动。

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.