RETROHIPPOCAMPAL CIRCUITS MEDIATED EPILEPTIFORM ACTIVITY

海马后回路介导的癫痫样活动

• 批准号: 6394050
• 负责人: MARK G STEWART
• 金额: $ 18.91万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6394050
• 关键词: Mammalia; brain electrical activity; brain mapping; electrophysiology; entorhinal cortex; histology; intercellular connection; neural information processing

DESCRIPTION: (Adapted from the Investigator's Abstract): The entorhinal cortex can generate epileptiform activity independent of the hippocampus, it can sustain epileptiform activity generated in the hippocampus, and it gates the spread of such activity to the neocortex. While there has been intensive work on the basis for epileptiform activity in CA3 and some phenomenological studies of the interactions of entorhinal and hippocampal seizure generators, there has been virtually no attention paid to the mechanism by which the retrohippocampal areas generate seizure activity themselves. Part of the reason for this has been a lack of data on the fundamental circuitry and cellular properties of retrohippocampal cells. Our laboratory has been studying the cells and circuits of the retrohippocampal regions, including entorhinal cortex, presubiculum, parasubiculum and subiculum. The aim of this project is to define the cells and intrinsic circuits of the entorhinal cortex and to identify their roles in the generation of epileptiform discharges. Our overall hypothesis is that epileptiform events (interictal spikes and after discharges) are generated in entorhinal cortex by a combination of intralaminar and interlaminar excitatory connections not found in other retrohippocampal or hippocampal structures. Single neurons will be electrophysiologically and morphologically characterized. The properties of unitary and compound excitatory postsynaptic potentials will be examined in identified cells. The cellular and synaptic properties of identified neurons will be correlated with their activity during epileptiform discharges in disinhibited slices. The results will provide fundamental data on the basic properties of cells in the entorhinal cortex and its intrinsic connectivity. These data will be part of the foundation for understanding the normal and abnormal physiology of the retrohippocampal regions. The properties of these cells and circuits they form in one model of epilepsy (that seen during disinhibition) will demonstrate some of the functional properties of the circuitry. These functional properties will provide critical insights into epileptogenesis and the spread of seizure activity in the entorhinal cortex. An understanding of such circuits may lead to practical strategies for limiting seizure generation and spread by targeted disconnection procedures.

描述：（改编自研究者摘要）：内嗅皮层 可以产生独立于海马体的癫痫样活动，它可以 维持海马体产生的癫痫样活动，并控制 将这种活动传播到新皮质。虽然工作很紧张 基于 CA3 的癫痫样活动和一些现象学研究 内嗅和海马癫痫发作发生器的相互作用 几乎没有人关注海马后区的机制 区域本身会产生癫痫发作活动。造成这种情况的部分原因有 缺乏有关基本电路和细胞特性的数据 海马后细胞。我们实验室一直在研究细胞和电路 海马后区域，包括内嗅皮质、前下皮质、 副下托和下托。 该项目的目的是定义细胞和内在电路 内嗅皮层并确定其在癫痫样生成中的作用 放电。我们的总体假设是癫痫样事件（发作间期） 尖峰和放电后）在内嗅皮层中由 未发现层内和层间兴奋性连接的组合 在其他海马后或海马结构中。单个神经元将 具有电生理学和形态学特征。的属性 单一和复合兴奋性突触后电位将在 识别出的细胞。已识别神经元的细胞和突触特性 将与它们在癫痫样放电期间的活动相关 去抑制切片。 结果将提供有关细胞基本特性的基础数据 内嗅皮层及其内在连接性。这些数据将成为 为了解正常和异常生理机能奠定基础 海马后区域。这些细胞及其形成的电路的特性 在一种癫痫模型中（在去抑制期间看到的）将表现出一些 电路的功能特性。这些功能特性将 提供对癫痫发生和癫痫发作传播的重要见解 内嗅皮层的活动。对此类电路的理解可能会导致 制定有针对性的限制癫痫发作和传播的实用策略 断开连接程序。