LOCAL INTERACTIONS BETWEEN HIPPOCAMPAL NEURONS

描述：(摘自申请者的摘要)大脑的长期后果 损伤是临床神经科学中的一个重要问题。一个重要的例子 兴奋性毒性神经退行性损伤，如对海马区的损害 长期癫痫持续状态的神经元，最终会导致 慢性癫痫。拟议的研究使用了来自 红藻氨酸治疗大鼠以确定癫痫持续状态如何导致 大鼠齿状回和CA1区局部突触回路的重组 海马体。焦点突触电流的全细胞膜片钳分析 笼中谷氨酸光解对海马神经元的微刺激，以及 双重录音将与解剖学技术相结合，以测试特定的 关于反复兴奋和抑制变化的假说。我们的目标是 确定癫痫持续状态后是否有进行性发展 导致海马区变化的新的异常突触回路 癫痫敏感度。尽管我们的主要重点将是评估更多 是否在脑内形成新的循环兴奋环路 癫痫持续状态后的海马区，并了解如何推定 这些回路密度的增加改变了海马体的特性 网络，申请者还将检查假设的变化在当地 抑制电路。申请者的目标是关注进步的本质 作为时间依赖模型的海马区突触重组 皮质网络的改变，可能发生在整个颞叶和 神经退行性脑损伤后的其他新皮质区域。

DESCRIPTION: (from applicant's abstract) The long-term consequences of brain injury are a critical problem in clinical neuroscience. One important example is how excitotoxic neurodegenerative lesions, such as damage to hippocampal neurons that occurs with prolonged status epilepticus, can ultimately lead to chronic epilepsy. The proposed studies use acute hippocampal slices from kainate-treated rats to determine how status epilepticus leads to the reorganization of local synaptic circuits in the dentate gyrus and CA1 areas of the hippocampus. Whole cell patch clamp analyses of synaptic currents, focal microstimulation of hippocampal neurons with photolysis of caged glutamate, and dual recordings will be combined with anatomic techniques to test specific hypotheses about changes in recurrent excitation and inhibition. We aim to determine whether status epilepticus is followed by a progressive development of new abnormal synaptic circuits that contribute to changes in hippocampal seizure susceptibility. Although our primary focus will be to evaluate more rigorously whether new recurrent excitatory circuits are formed in the hippocampus after status epilepticus, and to understand how the putative increase in density of these circuits alters the properties of hippocampal networks, the applicants will also examine hypothetical changes in local inhibitory circuits. The applicants aim to focus on the progressive nature of the synaptic reorganization of the hippocampus as a model for time-dependent changes in cortical networks that may occur throughout the temporal lobe and other neocortical areas after neurodegenerative brain injuries.