Cellular mechanisms of Pathological high frequency oscillations (pHFO) In Vitro

高频振荡（HFO），包括纹波，与明确的神经元事件相关， 通常记录在内侧颞叶（MTL）的某些部分，如CA 1区和 下托显然，这种振荡在正常情况下是不能在齿状回中观察到的。 脑回，但在癫痫发生过程中，该结构容易产生HFO。因为他们的 与MTL癫痫（MTLE）密切相关，齿状回的HFO应始终被认为是 病态的此外，MTLE相关的HFO在CA 1和下托中的发生率较高， 也可能与正常条件下观察到的HFO显著不同。与MTLE相关的 病理性HFO（pHFO），由100-200 Hz范围内的病理性纹波（pR）和快速 致痫结构中200-500 Hz范围内的波纹（FR）反映了基本的神经元机制 导致癫痫的发展和自发性癫痫的产生。由于抑制 中间神经元在这些同步事件的表现中发挥着重要作用， 该提案的目的包括一系列紧密整合的平行体外切片研究， MTLE患者和来自这种病症的实验动物模型：匹鲁卡品治疗的（PILO） 老鼠.目标是i）识别和表征主要神经元和特定神经元中的改变。 导致重新组装成能够产生pHFO的病理网络的中间神经元的亚类; ii） 检测特定中间神经元的消融和刺激对pHFO产生的影响。整体 这一假设是继发性的变化，内在神经元兴奋性和互连过程中， 癫痫发生的过程，激活和尖峰的模式，不同于控制条件，在特定的 中间神经元和主细胞有助于pHFO的产生。在一些MTL结构（例如，CA1 和下托），参与pHFO生成的细胞组装体可能与在pHFO生成期间活性的细胞组装体不同。 生理涟漪活动。在齿状回，通常没有HFO产生细胞 组装，特定的中间神经元和齿状回颗粒细胞（DGGC）的病理性重组 进入能够产生pHFO的癫痫细胞集合体是癫痫发生的关键组成部分， constitute.one这一病理过程的最早事件。因此，确定进展，目标， 这种病理细胞聚集的机制将为预防和可能的预防提供重要线索。 甚至逆转了癫痫的过程

High-frequency oscillations (HFO) including Ripples are associated with well-defined neuronal events and are commonly recorded in certain parts of the mesial temporal lobe (MTL) such as the CA1 region and the subiculum. Conspicuously, such oscillations cannot be observed under normal conditions in the dentate gyrus, but this structure will readily produce HFO during the process of epileptogenesis. Because of their tight association with MTL epilepsy (MTLE), HFO of the dentate gyrus should always be considered to be pathological. Moreover, the MTLE-associated HFO observed with high incidence in the CA1 and subiculum may also significantly differ from the HFO seen under normal conditions. The MTLE-associated pathological HFO (pHFO) consisting of pathological Ripples (pR) in the range of 100-200 Hz and Fast Ripples (FR) in the range of 200-500 Hz in epileptogenic structures reflect fundamental neuronal mechanisms responsible for the development of epilepsy and the generation of spontaneous seizures. Since inhibitory interneurons play a prominent role in the manifestation of these synchronous events, the immediate research objectives of this proposal consist of a series of tightly integrated parallel in vitro studies in slices from MTLE patients and from an experimental animal model of this condition: the pilocarpine-treated (PILO) mouse. The goals are i) to identify and characterize the alterations in principal neurons and in specific subclasses of interneurons leading to re-assembly into pathological networks capable of generating pHFO; ii) to examine the effects of ablation and stimulation of specific interneurons on pHFO generation. The overall hypothesis is that secondary to changes in intrinsic neuronal excitability and interconnections during the process of epileptogenesis, patterns of activation and spiking, that differ from control conditions, in specific interneurons and principal cells contribute to the generation of pHFO. In some MTL structures (e.g., CA1 and subiculum), the cell assemblies involved in pHFO generation may not be the same as those active during physiological Ripple activity. In the dentate gyrus, where normally there are no HFO generating cell assemblies, a pathological reorganization of specific interneurons and dentate gyrus granule cells (DGGC) into epileptic cell assemblies capable of generating pHFO is a critical component of epileptogenesis and may constitute.one of the earliest events of this pathological process. Thus, identifying the progression, targets, and mechanisms of such pathological cell assemblies will yield important clues for preventing and possibly even reversing the epileptogenic process.