SYNAPTIC MECHANISMS OF EPILEPTIFORM SYNCHRONIZATION

海马体对生理（θ节律）和 病理生理学（癫痫样活动）形式的神经元 同步这项建议旨在研究突触机制 参与产生异常的癫痫样活动， 海马切片制备。海马切片不能有 行为癫痫发作，但它可以显示异常的神经元同步 类似于记录的发作期和发作间期癫痫样放电， vivo.切片制备提供了研究细胞的机会， 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 去极化移位（PDS），发作间期的细胞内相关物， 放电，这可以通过减少突触抑制产生 由GABA介导或减少某些钾电流。的PDS 由任一类惊厥剂产生的， 发生突触电位，并代表网络现象。目标 这个建议的一个重要方面是揭示突触传递在神经元中的作用。 癫痫样活动模式的表达和调节（发作间期 和发作）。实验将使用细胞内电压和电流钳 记录技术和细胞外监测的神经元 人口反应。第一个具体目标是将 后超极化，遵循PDS的特点， 自发性癫痫样活动，定义为： 发作间期放电和发作样放电的产生。的 第二个具体目标是确定突触的贡献， 传递，特别是抑制性突触传递，在 同步发作模式的产生。第三个具体目标是 为了表征CA3中的复发性兴奋性突触连接， 损伤穹窿携带的海马传入神经后的子域 （主要是连合和胆碱能传入），并定义如何 病变的后遗症可能会增加癫痫样发作的倾向 同步这项建议的基本前提是， 了解海马体中的癫痫样活动，不仅会 为癫痫的临床治疗提供更好的设计依据，同时也是 突触机制，有助于正常同步神经元 活动可以更好地理解。

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.