NEURONAL PLASTICITY IN IN VITRO EPILEPTOGENESIS

体外癫痫发生的神经元可塑性

• 批准号: 3477893
• 负责人: LESLIE SARGENT JONES
• 金额: $ 7.76万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-20 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3477893
• 关键词: cellular pathology; cycloheximide; dendrites; disease /disorder model; electrical potential; electrophysiology; epilepsy; extracellular matrix; hippocampus; intracellular membranes; laboratory rat; learning; microelectrodes; microscopy; neural plasticity; neuroanatomy; proline; protein biosynthesis; pyramidal cells; silver impregnation

The research in this proposal is designed to test the hypothesis that the long-lasting character of stimulus train-induced bursting (STIB), a model for epilepsy, is protein synthesis dependent and correlated with morphologic changes. By appropriate tetanic stimulation of input and recurrent pathways, both CA1 and CA3 subfields of hippocampus may be induced to fire spontaneous, epileptiform bursts of field potentials; this can be produced in vitro in the hippocampal slice and the change in excitability generally lasts for the life of the slice (about 10 hours). The baseline characteristics of this hyperexcitability in both subfields will be examined electrophysiologically both extra- and intracellularly, and these results will be correlated with differences in dendritic spine number and shape between control and bursting slices. Further, the parameters for and results of STIB will be compared to those of long-term potentiation (LTP), a model for learning that depends on stimulus tetany to produce response potentiation; the two models differ only slightly in their stimulus parameters, yet this results in functionally critical differences in excitability. Once this fundamental information is collected, further studies will test the hypotheses that: protein synthesis is necessary for the long-term maintenance of STIB in CA1 and CA3; STID and LTP have a parallel course of development temporally, and the difference between the development of LTP and STIB in hippocampal pyramidal neurons is a threshold effect; the intracellular responses of hippocampal pyramidal neurons during the development and maintenance of LTP and STIB differ quantitatively rather than qualitatively; the development and maintenance of STIB in the hippocampus produces changes in the shape and possibly the number of dendritic spines in the stimulated subfields, the specific examination beginning with the apical dendrites of pyramidal neurons in CAl; some of the changes in dendritic spine morphology are protein synthesis-dependent; and, some of the proteins synthesized in association with STIB subserve the plasticity of both LTP and STIB. In each case, regardless of whether the hypothesis is correct or not, the outcome will yield valuable information on cellular processes that are relevant to epilepsy, learning and memory, or both.

该提案中的研究旨在检验以下假设 刺激列车引起的爆发（STIB）的长期特征，模型 对于癫痫，是蛋白质的合成，并与 形态学变化。通过适当对输入和 复发途径，海马的CA1和CA3子场均可能是 诱导火灾自发的癫痫样爆发；这 可以在海马切片中在体外产生，并变化 兴奋性通常可以持续使用切片的寿命（大约10个小时）。 这两个子字段中这种过度兴奋性的基线特征 将在电生理学上进行外部和细胞内检查， 这些结果将与树突状脊柱的差异相关 控制和爆破切片之间的数字和形状。此外， 将STIB的参数和结果进行比较 增强（LTP），一种学习模型，取决于刺激的破坏 产生响应增强；这两种模型在它们的中只有略有不同 刺激参数，但这会导致功能上关键的差异 兴奋性。 一旦收集了这些基本信息，进一步的研究将测试 假设：长期蛋白质合成是必要的 在CA1和CA3中维持STIB； STID和LTP的平行路线 暂时发展以及LTP的发展之间的差异 海马锥体神经元中的STIB是阈值。这 海马锥体神经元的细胞内反应 LTP和STIB的开发和维护在定量上有所不同 比定性； Stib的开发和维护 海马会产生形状的变化，甚至可能 刺激子场中的树突状刺，特定的检查 从Cal中的锥体神经元的顶端树突开始；其中一些 树突状脊柱形态的变化是蛋白质合成依赖性的。 并且，与Stib合成的某些蛋白质均得到 LTP和Stib的可塑性。在每种情况下，无论是否 假设是否正确，结果将产生有价值的信息 关于与癫痫，学习和记忆有关的细胞过程， 或两者兼而有之。